Skip to main content

Full text of "Cannabinoid Wikibook Essential Etheric Oils"

See other formats


Essential Etheric Oils 



PDF generated using the open source mwlib toolkit. See http://code.pediapress.com/ for more information. 
PDF generated at: Mon, 03 Jun 2013 00:23:44 UTC 



Contents 

Articles 

Cannabinoid 1 

Distillation 11 

Essential oil 25 

Hash oil 32 

Liquid-liquid extraction 34 

Medical cannabis 40 

References 

Article Sources and Contributors 66 

Image Sources, Licenses and Contributors 68 

Article Licenses 

License 70 



Cannabinoid 



Cannabinoid 



Cannabinoids are a class of diverse chemical compounds that activate cannabinoid receptors on cells that repress 
neurotransmitter release in the brain. These receptor proteins include the endocannabinoids (produced naturally in 
the body by humans and animals), the phytocannabinoids (found in cannabis and some other plants), and synthetic 
cannabinoids (produced chemically by humans). The most notable cannabinoid is the phytocannabinoid 
A -tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis. Cannabidiol (CBD) is another 
major constituent of the plant, representing up to 40% in its extracts. There are at least 85 different cannabinoids 
isolated from cannabis, exhibiting varied effects. 

Synthetic cannabinoids encompass a variety of distinct chemical classes: the classical cannabinoids structurally 
related to THC, the nonclassical cannabinoids (cannabimimetics) including the aminoalkylindoles, 
1,5 -diary lpyrazoles, quinolines, and arylsulphonamides, as well as eicosanoids related to the endocannabinoids. 

Cannabinoid receptors 

Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via 
nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors. The 
discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common 
in animals, and have been found in mammals, birds, fish, and reptiles. At present, there are two known types of 

cannabinoid receptors, termed CB and CB , with mounting evidence of more. The human brain has more 

n 
cannabinoid receptors than any other G protein-coupled receptor (GPCR) type. 

Cannabinoid receptor type 1 

CB receptors are found primarily in the brain, to be specific in the basal ganglia and in the limbic system, including 
the hippocampus. They are also found in the cerebellum and in both male and female reproductive systems. CB 
receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and 
cardiovascular functions. Thus, there is not the risk of respiratory or cardiovascular failure that can be produced by 
some drugs. CB receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis. 

Cannabinoid receptor type 2 

CB receptors are predominantly found in the immune system, or immune-derived cells with the greatest density in 

the spleen. While found only in the peripheral nervous system, a report does indicate that CB is expressed by a 

n 
subpopulation of microglia in the human cerebellum . CB receptors appear to be responsible for the 

n 

anti-inflammatory and possibly other therapeutic effects of cannabis. 



Phytocannabinoids 



Cannabinoid 



Type 



Cannabigerol-type 
CBG 



Cannabichromene-type 
CBC 



Cannabidiol-type 
CBD 



Tetrahydrocannabinol- 

and 

Cannabinol-type 

THC, CBN 



Cannabielsoin-type 
CBE 



iso- 

Tetrahydrocannabinol- 

type 

wo-THC 



Cannabicyclol-type 
CBL 



Cannabicitran-type 
CBT 



Skeleton 



Cyclization 

















Main classes of natural cannabinoids 



Phytocannabinoids (also called natural cannabinoids, herbal 
cannabinoids, and classical cannabinoids) are known to occur in 
several different plant species. These include Cannabis sativa, 
Cannabis indica, Cannabis ruderalis, Echinacea purpurea, Echinacea 
angustifolia, Echinacea pallida, Acmella oleracea, Helichrysum 
umbraculigerum, and Radula marginata. The best known herbal 
cannabinoids are A9-tetrahydrocannabinol (THC) from Cannabis and 
the lipophilic alkamides (alkylamides) from Echinacea species. 



[] 




At least 85 different cannabinoids have been isolated from the 

Cannabis plant and 25 different cannabinoids from Echinacea 

species. In Cannabis, these cannabinoids are concentrated in a 

viscous resin produced in structures known as glandular trichomes. In 

Echinacea species, cannabinoids are found throughout the plant 

structure, but are most concentrated in the roots and stems. Tea (Camellia sinensis) catechins have an affinity for 

human cannabinoid receptors. 



The bud of a Cannabis sativa flower coated with 
THC-laden trichomes 



[] 



Cannabinoid 




Cannabis indica plant 



Phytocannabinoids are nearly insoluble in water but are soluble in 
lipids, alcohols, and other non-polar organic solvents. However, as 
phenols, they form more water-soluble phenolate salts under strongly 
alkaline conditions. 

All-natural cannabinoids are derived from their respective 2-carboxylic 
acids (2-COOH) by decarboxylation (catalyzed by heat, light, or 
alkaline conditions). 

Cannabis-derived cannabinoids 

Types 

To the right, the main classes of cannabinoids from Cannabis are 
shown. All classes derive from cannabigerol-type compounds and 
differ mainly in the way this precursor is cyclized. 

Tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) (derived from Cannabis)', and 
dodeca-2E,4E,8Z,10E/Z-tetraenoic-acid-isobutylamides (the main bioactive constituents from Echinacea species) 
are the most prevalent natural cannabinoids and have received the most study. 

CBG (Cannabigerol) 

CBC (Cannabichromene) 

CBL (Cannabicyclol) 

CBV (Cannabivarin) 

THCV (Tetrahydrocannabivarin) 

CBDV (Cannabidivarin) 

CBCV (Cannabichromevarin) 

CBGV (Cannabigerovarin) 

CBGM (Cannabigerol Monomethyl Ether) 

Tetrahydrocannabinol 

Tetrahydrocannabinol (THC) is the primary psychoactive component of the Cannabis plant. 

9 8 

Z)e/ta-9-tetrahydrocannabinol (A -THC, THC) and delta- 8 -tetrahydrocannabinol (A -THC), mimic the action of 

anandamide, a neurotransmitter produced naturally in the body. These two THC's produce the effects associated with 

cannabis by binding to the CB cannabinoid receptors in the brain. THC appears to ease moderate pain (analgesic) 

and to be neuroprotective. Studies show THC reduces neuroinflammation and stimulates neurogenesis. THC 



has approximately equal affinity for the CB and CB receptors 



[8] 



Cannabidiol 

Cannabidiol (CBD) is not psychoactive, and was thought not to affect the psychoactivity of THC. However, recent 
evidence shows that smokers of cannabis with a higher CBD/THC ratio were less likely to experience 
schizophrenia-like symptoms. This is supported by psychological tests, in which participants experience less 
intense psychotic-like effects when intravenous THC was co-administered with CBD (as measured with a PANSS 
test). Cannabidiol has little affinity for CB and CB receptors but acts as an indirect antagonist of cannabinoid 

12 

agonists. Recently it was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR 
expressed in the caudate nucleus and putamen. Cannabidiol has also been shown to act as a 5-HT receptor 
agonist, an action that is involved in its antidepressant, anxiolytic, and neuroprotective effects. 



Cannabinoid 



It appears to relieve convulsion, inflammation, anxiety, and nausea. CBD has a greater affinity for the CB receptor 
than for the CB receptor. 

CBD shares a precursor with THC and is the main cannabinoid in low-THC Cannabis strains. CBD apparently plays 
a role in preventing the short-term memory loss associated with THC in mammals. 

Some research suggests that the antipsychotic effects of cannabidiol potentially represent a novel mechanism in the 
treatment of schizophrenia. 

Researchers at California Pacific Medical Center discovered CBD's ability to "turn off" the activity of ID1, the gene 
responsible for metastasis in breast and other types of cancers, including the particularly aggressive triple negative 
breast cancer. The researchers hope to start human trials soon. 

Cannabinol 

Cannabinol (CBN) is the primary product of THC degradation, and there is usually little of it in a fresh plant. CBN 
content increases as THC degrades in storage, and with exposure to light and air. It is only mildly psychoactive. Its 
affinity to the CB receptor is higher than for the CB receptor. 

Cannabigerol 

Cannabigerol (CBG) is non-psychotomimetic but still affects the overall effects of Cannabis. It acts as an 
a -adrenergic receptor agonist, 5-HT receptor antagonist, and CB receptor antagonist. It also binds to the CB 

2 1A 1 2 

receptor. 

Tetrahydrocannabivarin 

Tetrahydrocannabivarin (THCV) is prevalent in certain central Asian and southern African strains of Cannabis. 
It is an antagonist of THC at CB receptors and attenuates the psychoactive effects of THC. 

Cannabidivarin 

Although cannabidivarin (CBDV) is usually a minor constituent of the cannabinoid profile, enhanced levels of 
CBDV have been reported in feral cannabis plants from the northwest Himalayas, and in hashish from Nepal. 

Cannabichromene 

Cannabichromene (CBC) is non-psychoactive and does not affect the psychoactivity of THC . 

Double bond position 

In addition, each of the compounds above may be in different forms depending on the position of the double bond in 
the alicyclic carbon ring. There is potential for confusion because there are different numbering systems used to 
describe the position of this double bond. Under the dibenzopyran numbering system widely used today, the major 

Q O 

form of THC is called A -THC, while the minor form is called A -THC. Under the alternate terpene numbering 
system, these same compounds are called A -THC and A -THC, respectively. 

Length 

Most herbal cannabinoid compounds are 21 -carbon compounds. However, some do not follow this rule, primarily 
because of variation in the length of the side-chain attached to the aromatic ring. In THC, CBD, and CBN, this 
side-chain is a pentyl (5 -carbon) chain. In the most common homologue, the pentyl chain is replaced with a propyl 
(3-carbon) chain. Cannabinoids with the propyl side-chain are named using the suffix varin, and are designated, for 
example, THCV, CBDV, or CBNV. 



Cannabinoid 



Cannabis plant profile 

Cannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. The mixture of 
cannabinoids produced by a plant is known as the plant's cannabinoid profile. Selective breeding has been used to 
control the genetics of plants and modify the cannabinoid profile. For example, strains that are used as fiber 
(commonly called hemp) are bred such that they are low in psychoactive chemicals like THC. Strains used in 
medicine are often bred for high CBD content, and strains used for recreational purposes are usually bred for high 
THC content or for a specific chemical balance. 

Quantitative analysis of a plant's cannabinoid profile is often determined by gas chromatography (GC), or more 
reliably by gas chromatography combined with mass spectrometry (GC/MS). Liquid chromatography (LC) 
techniques are also possible, and, unlike GC methods, can differentiate between the acid and neutral forms of the 
cannabinoids. There have been systematic attempts to monitor the cannabinoid profile of cannabis over time, but 
their accuracy is impeded by the illegal status of the plant in many countries. 

Pharmacology 

Cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, 
sublingual absorption, or rectal suppository. Once in the body, most cannabinoids are metabolized in the liver, 
especially by cytochrome P450 mixed-function oxidases, mainly CYP 2C9. Thus supplementing with CYP 2C9 
inhibitors leads to extended intoxication. 

9 9 

Some is also stored in fat in addition to being metabolized in liver. A -THC is metabolized to 11-hydroxy-A -THC, 

which is then metabolized to 9-carboxy-THC. Some cannabis metabolites can be detected in the body several weeks 

after administration. These metabolites are the chemicals recognized by common antibody-based "drug tests"; in the 

case of THC et al., these loads do not represent intoxication (compare to ethanol breath tests that measure 

instantaneous blood alcohol levels) but an integration of past consumption over an approximately month-long 

window. 

Plant synthesis 

Cannabinoid production starts when an enzyme causes geranyl pyrophosphate and olivetolic acid to combine and 
form CBG. Next, CBG is independently converted to either CBD or CBC by two separate synthase enzymes. CBD is 
then enzymatically cyclized to THC. For the propyl homologues (THCV, CBDV and CBNV), there is a similar 
pathway that is based on CBGV. Recent studiesWikipedia: Avoid weasel words show that THC is not cyclized from 
CBD but rather directly from CBG. No experiment thus far has turned up an enzyme that converts CBD into THC, 
although it is still hypothesizedWikipedia:Avoid weasel words. 

Separation 

Cannabinoids can be separated from the plant by extraction with organic solvents. Hydrocarbons and alcohols are 
often used as solvents. However, these solvents are flammable and many are toxic. Butane may be used, which 
evaporates extremely quickly. Supercritical solvent extraction with carbon dioxide is an alternative technique. 
Although this process requires high pressures (73 atmospheres or more), there is minimal risk of fire or toxicity, 
solvent removal is simple and efficient, and extract quality can be well controlled. Once extracted, cannabinoid 
blends can be separated into individual components using wiped film vacuum distillation or other distillation 
techniques. However, to produce high-purity cannabinoids, chemical synthesis or semisynthesis is generally 
required. 



Cannabinoid 



Natural occurrence 

Cannabis indica may have a CBD:THC ratio 4-5 times that of Cannabis sativa. 

History 

Cannabinoids were first discovered in the 1940s, when CBD and CBN were identified. The structure of THC was 
first determined in 1964. 

Due to molecular similarity and ease of synthetic conversion, CBD was originally believed to be a natural precursor 
to THC. However, it is now known that CBD and THC are produced independently in the cannabis plant from the 
precursor CBG. 



Endocannabinoids 

Endocannabinoids are substances produced from within the body that 
activate cannabinoid receptors. After the discovery of the first 
cannabinoid receptor in 1988, scientists began searching for an 
endogenous ligand for the receptor. 

Types of endocannabinoid ligands 

Arachidonoylethanolamine (Anandamide or AEA) 

In 1992, in Raphael Mechoulam's lab, the first such compound was 

identified as arachidonoyl ethanolamine and named anandamide, a 

name derived from the Sanskrit word for bliss and -amide. Anandamide is derived from the essential fatty acid 

arachidonic acid. It has a pharmacology similar to THC, although its chemical structure is different. Anandamide 

binds to the central (CB ) and, to a lesser extent, peripheral (CB ) cannabinoid receptors, where it acts as a partial 

n 
agonist. Anandamide is about as potent as THC at the CB receptor. Anandamide is found in nearly all tissues in a 

wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate. 

Two analogs of anandamide, 7,10,13,16-docosatetraenoylethanolamide and /z6>m6>-y-linolenoylethanolamine, have 
similar pharmacology. All of these are members of a family of signalling lipids called Af-acylethanolamines, which 
also includes the noncannabimimetic palmitoylethanolamide and oleoylethanolamide, which possess 
anti-inflammatory and orexigenic effects, respectively. Many Af-acylethanolamines have also been identified in plant 
seeds and in molluscs. J 




2-arachidonoyl glycerol (2- AG) 

Another endocannabinoid, 2-arachidonoyl glycerol, binds to both the CB and CB receptors with similar affinity, 
acting as a full agonist at both. 2- AG is present at significantly higher concentrations in the brain than 
anandamide, and there is some controversy over whether 2- AG rather than anandamide is chiefly responsible for 
endocannabinoid signalling in vivo. In particular, one in vitro study suggests that 2- AG is capable of stimulating 
higher G-protein activation than anandamide, although the physiological implications of this finding are not yet 
known. 



Cannabinoid 



2-arachidonyl glyceryl ether (noladin ether) 

In 2001, a third, ether- type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), was isolated from porcine 
brain. Prior to this discovery, it had been synthesized as a stable analog of 2-AG; indeed, some controversy 
remains over its classification as an endocannabinoid, as another group failed to detect the substance at "any 
appreciable amount" in the brains of several different mammalian species. It binds to the CB cannabinoid receptor 
(K. = 21.2 nmol/L) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It 
binds primarily to the CB receptor, and only weakly to the CB receptor. 



N-arachidonoyl-dopamine (NADA) 

Discovered in 2000, NADA preferenti 

nr23i 
for the vanilloid receptor subtype 1 (TRPV1), a member of the vanilloid receptor family. 



[22] 
Discovered in 2000, NADA preferentially binds to the CB receptor. Like anandamide, NADA is also an agonist 



Virodhamine (OAE) 

A fifth endocannabinoid, virodhamine, or O-arachidonoyl-ethanolamine (OAE), was discovered in June 2002. 
Although it is a full agonist at CB and a partial agonist at CB it behaves as a CB antagonist in vivo. In rats, 
virodhamine was found to be present at comparable or slightly lower concentrations than anandamide in the brain, 
but 2- to 9-fold higher concentrations peripherally. 

Lysophosphatidylinositol (LPI) 

Recent evidence has highlighted LPI as the endogenous ligand to novel endocannabinoid receptor GPR55, making it 
a strong contender as the sixth endocannabinoid. 

Function 

Endocannabinoids serve as intercellular 'lipid messengers', signaling molecules that are released from one cell and 
activating the cannabinoid receptors present on other nearby cells. Although in this intercellular signaling role they 
are similar to the well-known monoamine neurotransmitters, such as acetylcholine and dopamine, endocannabinoids 
differ in numerous ways from them. For instance, they are used in retrograde signaling between neurons. 
Furthermore, endocannabinoids are lipophilic molecules that are not very soluble in water. They are not stored in 
vesicles, and exist as integral constituents of the membrane bilayers that make up cells. They are believed to be 
synthesized 'on-demand' rather than made and stored for later use. The mechanisms and enzymes underlying the 
biosynthesis of endocannabinoids remain elusive and continue to be an area of active research. 

The endocannabinoid 2-AG has been found in bovine and human maternal milk. 

Retrograde signal 

Conventional neurotransmitters are released from a presynaptic' cell and activate appropriate receptors on a 
postsynaptic' cell, where presynaptic and postsynaptic designate the sending and receiving sides of a synapse, 
respectively. Endocannabinoids, on the other hand, are described as retrograde transmitters because they most 
commonly travel 'backward' against the usual synaptic transmitter flow. They are, in effect, released from the 
postsynaptic cell and act on the presynaptic cell, where the target receptors are densely concentrated on axonal 
terminals in the zones from which conventional neurotransmitters are released. Activation of cannabinoid receptors 
temporarily reduces the amount of conventional neurotransmitter released. This endocannabinoid mediated system 
permits the postsynaptic cell to control its own incoming synaptic traffic. The ultimate effect on the 
endocannabinoid-releasing cell depends on the nature of the conventional transmitter being controlled. For instance, 
when the release of the inhibitory transmitter GAB A is reduced, the net effect is an increase in the excitability of the 
endocannabinoid-releasing cell. On the converse, when release of the excitatory neurotransmitter glutamate is 
reduced, the net effect is a decrease in the excitability of the endocannabinoid-releasing cell. 



Cannabinoid 



Range 

Endocannabinoids are hydrophobic molecules. They cannot travel unaided for long distances in the aqueous medium 
surrounding the cells from which they are released, and therefore act locally on nearby target cells. Hence, although 
emanating diffusely from their source cells, they have much more restricted spheres of influence than do hormones, 
which can affect cells throughout the body. 

Synthetic cannabinoids 

Historically, laboratory synthesis of cannabinoids were often based on the structure of herbal cannabinoids, and a 
large number of analogs have been produced and tested, especially in a group led by Roger Adams as early as 1941 
and later in a group led by Raphael Mechoulam. Newer compounds are no longer related to natural cannabinoids or 
are based on the structure of the endogenous cannabinoids. 

Synthetic cannabinoids are particularly useful in experiments to determine the relationship between the structure and 
activity of cannabinoid compounds, by making systematic, incremental modifications of cannabinoid molecules. 

Medications containing natural or synthetic cannabinoids or cannabinoid analogs: 

• Dronabinol (Marinol), is A -tetrahydrocannabinol (THC), used as an appetite stimulant, anti-emetic, and 
analgesic 

• Nabilone (Cesamet), a synthetic cannabinoid and an analog of Marinol. It is Schedule II unlike Marinol, which is 
Schedule III 

• Sativex, a cannabinoid extract oral spray containing THC, CBD, and other cannabinoids used for neuropathic pain 
and spasticity in 22 countries including England, Canada and Spain. Sativex develops whole-plant cannabinoid 
medicines 

• Rimonabant (SR141716), a selective cannabinoid (CB ) receptor inverse agonist once used as an anti-obesity 
drug under the proprietary name Acomplia. It was also used for smoking cessation 

Other notable Wikipedia:Please clarify synthetic cannabinoids include: 

• JWH-018, a potent synthetic cannabinoid agonist discovered by Dr. John W. Huffman at Clemson University. It 
is being increasingly sold in legal smoke blends collectively known as "spice". Several countries and states have 
moved to ban it legally. 
JWH-073 

CP-55940, produced in 1974, this synthetic cannabinoid receptor agonist is many times more potent than THC. 
Dimethylheptylpyran 

HU-210, about 100 times as potent as THC [27] 

HU-331 a potential anti-cancer drug derived from cannabidiol that specifically inhibits topoisomerase II. 
SR144528, a CB receptor antagonist 
WIN 55,212-2, a potent cannabinoid receptor agonist 
JWH-133, a potent selective CB receptor agonist 

Levonantradol (Nantrodolum), an anti-emetic and analgesic but not currently in use in medicine 
AM-2201, a potent cannabinoid receptor agonist. 



Cannabinoid 



References 

[2] http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1962-01-01_3_page005.html 

[5] Alzheimer's disease; taking the edge off with cannabinoids? - Campbell - 2009 - British Journal of Pharmacology - Wiley Online Library 

(http://onlinelibrary.wileyx 
[6] A Molecular Link between the Active Component of Marijuana and Alzheimer's Disease Pathology - Molecular Pharmaceutics (ACS 

Publications) (http://pubs.acs.org/doi/abs/10. 1021/mp060066m) 
[7] JCI - Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects (http:// 

www.jci.org/articles/view/25509) 
[10] Translational Psychiatry - Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia (http://www. 

nature.com/tp/journal/v2/n3/full/tp201215a.html) 
[11] Pot compound seen as tool against cancer - SFGate (http://www.sfgate.com/health/article/ 

Pot-compound-seen-as-tool-against-cancer-3875562.php#ixzz2GZmg5kGr) 
[12] Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells (http://mct.aacrjournals.0rg/content/6/l 1/ 

2921. abstract) 
[13] Antitumor activity of plant cannabinoid... [J Pharmacol Exp Ther. 2006] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/ 

16728591) 
[14] Marijuana Compound Fights Cancer; Human Trials Next I NBC Bay Area (http://www.nbcbayarea.com/news/local/ 

Marijuana-Compound-Fights-Cancer-Human-Trials-Next- 170406 1 16.html) 
[15] Baker, P.B., T.A. Gough and B.J. Taylor. 1980. Illicitly imported Cannabis products: some physical and chemical features indicative of their 

origin. Bulletin on Narcotics 32(2): 31-40. 
[22] Bisogno, T., D. Melck, M. Bobrov, N. M. Gretskaya, V. V. Bezuglov, L. De Petrocellis, V. Di Marzo. "N-acyl-dopamines: novel synthetic 

CB cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo." The 

Biochemical Journal 2000 Nov 1;351 Pt 3:817-24. PMID 11042139 
[27] http://www.marijuana.org/mydnal0-12-05.htm 

Further reading 

• De Meijer, E. P.; Bagatta, M.; Carboni, A.; Crucitti, P.; Moliterni, V. M.; Ranalli, P.; Mandolino, G. (2003). "The 
inheritance of chemical phenotype in Cannabis sativa L" (http://www.ncbi.nlm.nih.gov/pmc/articles/ 
PMC1462421). Genetics 163 (1): 335-346. PMC 1462421 (http://www.ncbi.nlm.nih.gov/pmc/articles/ 
PMC1462421). PMID 12586720 (http://www.ncbi.nlm.nih.gov/pubmed/12586720). 

• Devane WA, Hanus L, Breuer A, et al. (1992). "Isolation and structure of a brain constituent that binds to the 
cannabinoid receptor". Science 258 (5090): 1946-9. doi: 10. 1126/science. 1470919 (http://dx.doi.org/10.1126/ 
science. 1470919). PMID 1470919 (http://www.ncbi.nlm.nih.gov/pubmed/1470919). 

• Elsohly MA, Slade D (2005). "Chemical constituents of marijuana: the complex mixture of natural cannabinoids". 
Life Sci. 78 (5): 539-48. doi: 10.1016/j.lfs.2005.09.011 (http://dx.doi.Org/10.1016/j.lfs.2005.09.011). 

PMID 16199061 (http://www.ncbi.nlm.nih.gov/pubmed/16199061). 

• Hanus L, Gopher A, Almog S, Mechoulam R (1993). "Two new unsaturated fatty acid ethanolamides in brain that 
bind to the cannabinoid receptor". /. Med. Chem. 36 (20): 3032-4. doi: 10.1021/jm00072a026 (http://dx.doi. 
org/10. 1021/jm00072a026). PMID 8411021 (http://www.ncbi.nlm.nih.gov/pubmed/8411021). 

• Hanus L (1987). "Biogenesis of cannabinoid substances in the plant". Acta Universitatis Palackianae 
Olomucensis Facultatis Medicae 116: 47-53. PMID 2962461 (http://www.ncbi.nlm.nih.gov/pubmed/ 
2962461). 

• Hanus, L., Krejci, Z. (1975). "Isolation of two new cannabinoid acids from Cannabis sativa L. of Czechoslovak 
origin". Acta Univ. Olomuc, Fac. Med 74: 161-166. 

• Hanus, L., Krejci, Z., Hruban, L. (1975). "Isolation of cannabidiolic acid from Turkish variety of cannabis 
cultivated for fibre". Acta Univ. Olomuc, Fac. Med 74: 167-172. 

• Kofalvi, A. (2008). Kofalvi, Attila, ed. Cannabinoids and the Brain, doi: 10.1007/978-0-387-74349-3 (http://dx. 
doi.org/10. 1007/978-0-387-74349-3). ISBN 978-0-387-74348-6. 



Cannabinoid 10 

• Mechoulam R, Ben-Shabat S, Hanus L, et al. (1995). "Identification of an endogenous 2-monoglyceride, present 
in canine gut, that binds to cannabinoid receptors". Biochem. Pharmacol 50 (1): 83-90. doi: 
10.1016/0006-2952(95)00109-D (http://dx.doi.org/10. 1016/0006-2952(95)00109-D). PMID 7605349 (http:/ 
/www. ncbi.nlm.nih.gov/pubmed/7605349). 

• Nicoll RA, Alger BE (2004). "The brain's own marijuana". Sci. Am. 291 (6): 68-75. doi: 

10. 103 8/scientificamerican 1204-68 (http://dx.doi.org/10. 1 03 8/scientificamerican 1204-68). PMID 15597982 
(http://www.ncbi.nlm.nih.gov/pubmed/15597982). 

• Racz, I.; Nadal, X.; Alferink, J.; Banos, J.; Rehnelt, J.; Martin, M.; Pintado, B.; Gutierrez-Adan, A. et al. (2008). 
"Interferon-gamma is a critical modulator of CB(2) cannabinoid receptor signaling during neuropathic pain". 
Journal of Neuroscience 28 (46): 12136-12145. doi: 10.1523/JNEUROSCI.3402-08.2008 (http://dx.doi.org/ 
10.1523/JNEUROSCI.3402-08.2008). PMID 19005078 (http://www.ncbi.nlm.nih.gov/pubmed/ 
19005078). 

• Racz, I.; Nadal, X.; Alferink, J.; Banos, J.; Rehnelt, J.; Martin, M.; Pintado, B.; Gutierrez-Adan, A. et al. (2008). 
"Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic 
pain". Journal of Neuroscience 28 (46): 12125-12135. doi: 10.1523/JNEUROSCI.3400-08.2008 (http://dx.doi. 
org/10. 1523/JNEUROSCI.3400-08.2008). PMID 19005077 (http://www.ncbi.nlm.nih.gov/pubmed/ 
19005077). 

• Turner, C. E., Mole, M. L., Hanus, L., ElSohly, H. N. (1981). "Constituents of Cannabis sativa L. XIX. Isolation 
and structure elucidation of cannabiglendol. A novel cannabinoid from an Indian variant" (http://pubs.acs.org/ 
cgi-bin/archive.cgi/jnprdf/1981/44/i01/pdf/np50013a005.pdf). /. Nat. Prod. 44 (1): 27-33. doi: 
10.1021/np50013a005 (http://dx.doi.org/10.1021/np50013a005). 

External links 

Cannabinoid information 

• Bela Szabo: Pharmacology of Cannabinoid Receptors (http://www.biotrend.com/download/ 
BT-Review_0208_Cannabinoids.pdf) BIOTREND Reviews No. 02, February 2008 

• Marijuana and Medicine - Assessing the Science Base (Institute of Medicine) - 1999 (http://books.nap.edu/ 
html/marimed/) at National Academies Press 

• House of Lords Report - Cannabis (United Kingdom) - 1998 (http://www.parliament.the-stationery-office.co. 
uk/pa/ldl99798/ldselect/ldsctech/151/15101.htm) at Parliament of the United Kingdom 

• Cannabis: A Health Perspective and Research Agenda - 1997 (http://whqlibdoc.who.int/hq/1997/ 
WHO_MSA_PSA_97.4.pdf) at World Health Organization 

• Chemical Ecology of Cannabis (J. Intl. Hemp Assn. - 1994) (http://www.hempfood.com/IHA/iha01201.html) 

• THC (tetrahydrocannabinol) accumulation in glands of Cannabis (Cannabaceae) (http://www.hempreport.com/ 
issues/17/malbodyl7.html) 

• Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb (PDF) (http://www. 
onlinepot.org/medical/Izzo Plant Cannabinoids Therapeutic Opportunities TIPS 2009.pdf) 



Cannabinoid 



11 



Cannabinoid research organizations 

• The International Cannabinoid Research Society (http://www.cannabinoidsociety.org) 

• The Canadian Consortium for the Investigation of Cannabinoids (http://www.ccic.net) 

• Therapeutic Potential in Spotlight at Cannabinoid Researchers' Meeting (http://www.ccrmg.org/journal/04spr/ 
potential.html) at California Cannabis Research Medical Group 

• International Cannabinoid Research Society (http://cannabinoidsociety.org/) 



Distillation 



Distillation is a method of separating mixtures based on differences in 
volatility of components in a boiling liquid mixture. Distillation is a 
unit operation, or a physical separation process, and not a chemical 
reaction. 

Commercially, distillation has a number of applications. It is used to 
separate crude oil into more fractions for specific uses such as 
transport, power generation and heating. Water is distilled to remove 
impurities, such as salt from seawater. Air is distilled to separate its 
components — notably oxygen, nitrogen, and argon — for industrial use. 
Distillation of fermented solutions has been used since ancient times to 
produce distilled beverages with a higher alcohol content. The 
premises where distillation is carried out, especially distillation of 
alcohol, are known as a distillery. A still is the apparatus used for 
distillation. 




/# #\ 



r. \ 13 



Laboratory display of distillation: 1: A heating 

device 2: Still pot 3: Still head 4: 

Thermometer/Boiling point temperature 5: 

Condenser 6: Cooling water in 7: Cooling water 

out 8: Distillate/receiving flask 9: Vacuum/gas 

inlet 10: Still receiver 11: Heat control 12: Stirrer 

speed control 13: Stirrer/heat plate 14: Heating 

(Oil/sand) bath 15: Stirring means e.g. (shown), 

boiling chips or mechanical stirrer 16: Cooling 

bath. [] 



Distillation 



12 



History 

The first clear evidence of distillation comes from Greek alchemists 
working in Alexandria in the 1st century AD. Distilled water has been 
known since at least c. 200, when Alexander of Aphrodisias described 
the process. Distillation in China could have begun during the Eastern 
Han Dynasty (lst-2nd centuries), but archaeological evidence 
indicates that actual distillation of beverages began in the Jin and 
Southern Song dynasties. A still was found in an archaeological site 
in Qinglong, Hebei province dating to the 12th century. Distilled 
beverages were more common during the Yuan dynasty. Arabs 
learned the process from the Egyptians and used it extensively in their 

i • ! . [citation needed] 

chemical experiments 

Clear evidence of the distillation of alcohol comes from the School of 
Salerno in the 12th century. Fractional distillation was developed 
by Tadeo Alderotti in the 13th century. 




Distillation apparatus of Zosimos of Panopolis, 

from Marcelin Berthelot, Collection des anciens 

alchimistes grecs (3 vol., Paris, 1887- 



[2] 



In 1500, German alchemist Hieronymus Braunschweig published Liber de arte destillandi (The Book of the Art of 
Distillation) the first book solely dedicated to the subject of distillation, followed in 1512 by a much expanded 
version. In 1651, John French published The Art of Distillation the first major English compendium of practice, 
though it has been claimed that much of it derives from Braunschweig's work. This includes diagrams with people 
in them showing the industrial rather than bench scale of the operation. 



As alchemy evolved into the science of chemistry, vessels called 
retorts became used for distillations. Both alembics and retorts are 
forms of glassware with long necks pointing to the side at a downward 
angle which acted as air-cooled condensers to condense the distillate 
and let it drip downward for collection. Later, copper alembics were 
invented. Riveted joints were often kept tight by using various 
mixtures, for instance a dough made of rye flour. These alembics 
often featured a cooling system around the beak, using cold water for 
instance, which made the condensation of alcohol more efficient. 
These were called pot stills. Today, the retorts and pot stills have been 
largely supplanted by more efficient distillation methods in most 
industrial processes. However, the pot still is still widely used for the 
elaboration of some fine alcohols such as cognac, Scotch whisky, 
tequila and some vodkas. Pot stills made of various materials (wood, 
clay, stainless steel) are also used by bootleggers in various countries. 




Small pot stills are also sold for the domestic production 
water or essential oils. 



[7] 



of flower 




Distillation 



Early forms of distillation were batch processes using one vaporization 
and one condensation. Purity was improved by further distillation of the condensate. Greater volumes were 
processed by simply repeating the distillation. Chemists were reported to carry out as many as 500 to 600 
distillations in order to obtain a pure compound. 



[8] 



Distillation 



13 



In the early 19th century the basics of modern techniques including 
pre-heating and reflux were developed, particularly by the French, 
then in 1830 a British Patent was issued to Aeneas Coffey for a 
whiskey distillation column, which worked continuously and may be 
regarded as the archetype of modern petrochemical units. In 1877, 
Ernest Solvay was granted a U.S. Patent for a tray column for 
ammonia distillation and the same and subsequent years saw 
developments of this theme for oil and spirits. 

With the emergence of chemical engineering as a discipline at the end 
of the 19th century, scientific rather than empirical methods could be 
applied. The developing petroleum industry in the early 20th century 
provided the impetus for the development of accurate design methods 
such as the McCabe-Thiele method and the Fenske equation. The 
availability of powerful computers has also allowed direct computer 
simulation of distillation columns. 




Old Ukrainian vodka still 




Simple liqueur distillation in East Timor 



Applications of distillation 

The application of distillation can roughly be divided in four groups: laboratory scale, industrial distillation, 
distillation of herbs for perfumery and medicinals (herbal distillate), and food processing. The latter two are 
distinctively different from the former two in that in the processing of beverages, the distillation is not used as a true 
purification method but more to transfer all volatiles from the source materials to the distillate. 

The main difference between laboratory scale distillation and industrial distillation is that laboratory scale distillation 
is often performed batch-wise, whereas industrial distillation often occurs continuously. In batch distillation, the 
composition of the source material, the vapors of the distilling compounds and the distillate change during the 
distillation. In batch distillation, a still is charged (supplied) with a batch of feed mixture, which is then separated 
into its component fractions which are collected sequentially from most volatile to less volatile, with the bottoms 
(remaining least or non-volatile fraction) removed at the end. The still can then be recharged and the process 
repeated. 

In continuous distillation, the source materials, vapors, and distillate are kept at a constant composition by carefully 
replenishing the source material and removing fractions from both vapor and liquid in the system. This results in a 
better control of the separation process. 



Idealized distillation model 

The boiling point of a liquid is the temperature at which the vapor pressure of the liquid equals the pressure in the 
liquid, enabling bubbles to form without being crushed. A special case is the normal boiling point, where the vapor 
pressure of the liquid equals the ambient atmospheric pressure. 

It is a common misconception that in a liquid mixture at a given pressure, each component boils at the boiling point 
corresponding to the given pressure and the vapors of each component will collect separately and purely. This, 
however, does not occur even in an idealized system. Idealized models of distillation are essentially governed by 
Raoult's law and Dalton's law, and assume that vapor-liquid equilibria are attained. 

Raoult's law assumes that a component contributes to the total vapor pressure of the mixture in proportion to its 
percentage of the mixture and its vapor pressure when pure, or succinctly: partial pressure equals mole fraction 
multiplied by vapor pressure when pure. If one component changes another component's vapor pressure, or if the 



Distillation 



14 



volatility of a component is dependent on its percentage in the mixture, the law will fail. 

Dalton's law states that the total vapor pressure is the sum of the vapor pressures of each individual component in the 
mixture. When a multi-component liquid is heated, the vapor pressure of each component will rise, thus causing the 
total vapor pressure to rise. When the total vapor pressure reaches the pressure surrounding the liquid, boiling occurs 
and liquid turns to gas throughout the bulk of the liquid. Note that a mixture with a given composition has one 
boiling point at a given pressure, when the components are mutually soluble. 

An implication of one boiling point is that lighter components never cleanly "boil first". At boiling point, all volatile 
components boil, but for a component, its percentage in the vapor is the same as its percentage of the total vapor 
pressure. Lighter components have a higher partial pressure and thus are concentrated in the vapor, but heavier 
volatile components also have a (smaller) partial pressure and necessarily evaporate also, albeit being less 
concentrated in the vapor. Indeed, batch distillation and fractionation succeed by varying the composition of the 
mixture. In batch distillation, the batch evaporates, which changes its composition; in fractionation, liquid higher in 
the fractionation column contains more lights and boils at lower temperatures. 

The idealized model is accurate in the case of chemically similar liquids, such as benzene and toluene. In other cases, 
severe deviations from Raoult's law and Dalton's law are observed, most famously in the mixture of ethanol and 
water. These compounds, when heated together, form an azeotrope, which is a composition with a boiling point 
higher or lower than the boiling point of each separate liquid. Virtually all liquids, when mixed and heated, will 
display azeotropic behaviour. Although there are computational methods that can be used to estimate the behavior of 
a mixture of arbitrary components, the only way to obtain accurate vapor-liquid equilibrium data is by measurement. 

It is not possible to completely purify a mixture of components by distillation, as this would require each component 
in the mixture to have a zero partial pressure. If ultra-pure products are the goal, then further chemical separation 
must be applied. When a binary mixture is evaporated and the other component, e.g. a salt, has zero partial pressure 
for practical purposes, the process is simpler and is called evaporation in engineering. 



Batch distillation 




A batch still showing the separation of A and B. 



Heating an ideal mixture of two volatile substances A and B (with A 
having the higher volatility, or lower boiling point) in a batch 
distillation setup (such as in an apparatus depicted in the opening 
figure) until the mixture is boiling results in a vapor above the liquid 
which contains a mixture of A and B. The ratio between A and B in the 
vapor will be different from the ratio in the liquid: the ratio in the 
liquid will be determined by how the original mixture was prepared, 
while the ratio in the vapor will be enriched in the more volatile 
compound, A (due to Raoult's Law, see above). The vapor goes 
through the condenser and is removed from the system. This in turn means that the ratio of compounds in the 
remaining liquid is now different from the initial ratio (i.e. more enriched in B than the starting liquid). 

The result is that the ratio in the liquid mixture is changing, becoming richer in component B. This causes the boiling 
point of the mixture to rise, which in turn results in a rise in the temperature in the vapor, which results in a changing 
ratio of A : B in the gas phase (as distillation continues, there is an increasing proportion of B in the gas phase). This 
results in a slowly changing ratio A : B in the distillate. 

If the difference in vapor pressure between the two components A and B is large (generally expressed as the 
difference in boiling points), the mixture in the beginning of the distillation is highly enriched in component A, and 
when component A has distilled off, the boiling liquid is enriched in component B. 



Distillation 15 

Continuous distillation 

Continuous distillation is an ongoing distillation in which a liquid mixture is continuously (without interruption) fed 
into the process and separated fractions are removed continuously as output streams as time passes during the 
operation. Continuous distillation produces at least two output fractions, including at least one volatile distillate 
fraction, which has boiled and been separately captured as a vapor condensed to a liquid. There is always a bottoms 
(or residue) fraction, which is the least volatile residue that has not been separately captured as a condensed vapor. 

Continuous distillation differs from batch distillation in the respect that concentrations should not change over time. 
Continuous distillation can be run at a steady state for an arbitrary amount of time. For any source material of 
specific composition, the main variables that affect the purity of products in continuous distillation are the reflux 
ratio and the number of theoretical equilibrium stages (practically, the number of trays or the height of packing). 
Reflux is a flow from the condenser back to the column, which generates a recycle that allows a better separation 
with a given number of trays. Equilibrium stages are ideal steps where compositions achieve vapor-liquid 
equilibrium, repeating the separation process and allowing better separation given a reflux ratio. A column with a 
high reflux ratio may have fewer stages, but it refluxes a large amount of liquid, giving a wide column with a large 
holdup. Conversely, a column with a low reflux ratio must have a large number of stages, thus requiring a taller 
column. 

General improvements 

Both batch and continuous distillations can be improved by making use of a fractionating column on top of the 
distillation flask. The column improves separation by providing a larger surface area for the vapor and condensate to 
come into contact. This helps it remain at equilibrium for as long as possible. The column can even consist of small 
subsystems ('trays' or 'dishes') which all contain an enriched, boiling liquid mixture, all with their own vapor-liquid 
equilibrium. 

There are differences between laboratory-scale and industrial- scale fractionating columns, but the principles are the 
same. Examples of laboratory- scale fractionating columns (in increasing efficiency) include: 

• Air condenser 

• Vigreux column (usually laboratory scale only) 

• Packed column (packed with glass beads, metal pieces, or other chemically inert material) 

• Spinning band distillation system. 



Distillation 



16 



Laboratory scale distillation 

Laboratory scale distillations are 
almost exclusively run as batch 
distillations. The device used in 
distillation, sometimes referred to as a 
still , consists at a minimum of a 
reboiler or pot in which the source 
material is heated, a condenser in 
which the heated vapour is cooled back 
to the liquid state, and a receiver in 
which the concentrated or purified 
liquid, called the distillate, is 
collected. Several laboratory scale 
techniques for distillation exist (see 
also distillation types). 

Simple distillation 




Typical laboratory distillation unit 



In simple distillation, the vapor is immediately channeled into a condenser. Consequently, the distillate is not pure 
but rather its composition is identical to the composition of the vapors at the given temperature and pressure. That 
concentration follows Raoult's law. 

As a result, simple distillation is effective only when the liquid boiling points differ greatly (rule of thumb is 
25 °C) or when separating liquids from non- volatile solids or oils. For these cases, the vapor pressures of the 
components are usually sufficiently different that the distillate may be sufficiently pure for its intended purpose. 



Fractional distillation 

For many cases, the boiling points of the components in the mixture will be sufficiently close that Raoult's law must 
be taken into consideration. Therefore, fractional distillation must be used in order to separate the components by 
repeated vaporization-condensation cycles within a packed fractionating column. This separation, by successive 
distillations, is also referred to as rectification. 

As the solution to be purified is heated, its vapors rise to the fractionating column. As it rises, it cools, condensing on 
the condenser walls and the surfaces of the packing material. Here, the condensate continues to be heated by the 
rising hot vapors; it vaporizes once more. However, the composition of the fresh vapors are determined once again 

by Raoult's law. Each vaporization-condensation cycle (called a theoretical plate) will yield a purer solution of the 

ri2i 
more volatile component. In reality, each cycle at a given temperature does not occur at exactly the same position 

in the fractionating column; theoretical plate is thus a concept rather than an accurate description. 

More theoretical plates lead to better separations. A spinning band distillation system uses a spinning band of Teflon 
or metal to force the rising vapors into close contact with the descending condensate, increasing the number of 
theoretical plates. 



[13] 



Distillation 



17 



Steam distillation 



n 



Like vacuum distillation, steam distillation is a method for distilling compounds which are heat- sensitive. The 
temperature of the steam is easier to control than the surface of a heating element, and allows a high rate of heat 
transfer without heating at a very high temperature. This process involves bubbling steam through a heated mixture 
of the raw material. By Raoult's law, some of the target compound will vaporize (in accordance with its partial 
pressure). The vapor mixture is cooled and condensed, usually yielding a layer of oil and a layer of water. 

Steam distillation of various aromatic herbs and flowers can result in two products; an essential oil as well as a 
watery herbal distillate. The essential oils are often used in perfumery and aromatherapy while the watery distillates 
have many applications in aromatherapy, food processing and skin care. 



Vacuum distillation 

Some compounds have very high boiling points. To boil such 
compounds, it is often better to lower the pressure at which such 
compounds are boiled instead of increasing the temperature. Once the 
pressure is lowered to the vapor pressure of the compound (at the given 
temperature), boiling and the rest of the distillation process can 
commence. This technique is referred to as vacuum distillation and it 
is commonly found in the laboratory in the form of the rotary 
evaporator. 

This technique is also very useful for compounds which boil beyond 
their decomposition temperature at atmospheric pressure and which 
would therefore be decomposed by any attempt to boil them under 
atmospheric pressure. 

Molecular distillation is vacuum distillation below the pressure of 
0.01 torr. 0.01 torr is one order of magnitude above high vacuum, 
where fluids are in the free molecular flow regime, i.e. the mean free 
path of molecules is comparable to the size of the equipment. The 
gaseous phase no longer exerts significant pressure on the substance to be evaporated, and consequently, rate of 
evaporation no longer depends on pressure. That is, because the continuum assumptions of fluid dynamics no longer 
apply, mass transport is governed by molecular dynamics rather than fluid dynamics. Thus, a short path between the 
hot surface and the cold surface is necessary, typically by suspending a hot plate covered with a film of feed next to a 
cold plate with a line of sight in between. Molecular distillation is used industrially for purification of oils. 




Dimethyl sulfoxide usually boils at 189 °C. 

Under a vacuum, it distills off into the receiver at 

only 70 °C. 



Air-sensitive vacuum distillation 

Some compounds have high boiling points as well as being air sensitive. A simple vacuum distillation system as 
exemplified above can be used, whereby the vacuum is replaced with an inert gas after the distillation is complete. 
However, this is a less satisfactory system if one desires to collect fractions under a reduced pressure. To do this a 



Distillation 



18 



"cow" or "pig" adaptor can be added to the end of the condenser, or for 
better results or for very air sensitive compounds a Perkin triangle 
apparatus can be used. 

The Perkin triangle, has means via a series of glass or Teflon taps to 
allows fractions to be isolated from the rest of the still, without the 
main body of the distillation being removed from either the vacuum or 
heat source, and thus can remain in a state of reflux. To do this, the 
sample is first isolated from the vacuum by means of the taps, the 
vacuum over the sample is then replaced with an inert gas (such as 
nitrogen or argon) and can then be stoppered and removed. A fresh 
collection vessel can then be added to the system, evacuated and linked 
back into the distillation system via the taps to collect a second 
fraction, and so on, until all fractions have been collected. 




Perkin triangle distillation setup 

1: Stirrer bar/anti-bumping granules 2: Still pot 
3: Fractionating column 4: Thermometer/Boiling 
point temperature 5: Teflon tap 1 6: Cold finger 

7: Cooling water out 8: Cooling water in 9: 

Teflon tap 2 10: Vacuum/gas inlet 11: Teflon tap 

3 12: Still receiver 



Short path distillation 

Short path distillation is a distillation technique that involves the 
distillate travelling a short distance, often only a few centimeters, and 
is normally done at reduced pressure. A classic example would be a 
distillation involving the distillate travelling from one glass bulb to 
another, without the need for a condenser separating the two chambers. 
This technique is often used for compounds which are unstable at high 
temperatures or to purify small amounts of compound. The advantage 
is that the heating temperature can be considerably lower (at reduced 
pressure) than the boiling point of the liquid at standard pressure, and 
the distillate only has to travel a short distance before condensing. A 
short path ensures that little compound is lost on the sides of the 
apparatus. The Kugelrohr is a kind of a short path distillation apparatus 
which often contain multiple chambers to collect distillate fractions. 

Zone distillation 



VJ 



\ 



r^5 



^ 





Short path vacuum distillation apparatus with 
vertical condenser (cold finger), to minimize the 

distillation path; 1: Still pot with stirrer 
bar/anti-bumping granules 2: Cold finger - bent 

to direct condensate 3: Cooling water out 4: 

cooling water in 5: Vacuum/gas inlet 6: Distillate 

flask/distillate. 



Zone distillation is a distillation process in long container with partial 

I i 

melting of refined matter in moving liquid zone and condensation of 

vapor in the solid phase at condensate pulling in cold area. The process is worked in theory. When zone heater is 

moving from the top to the bottom of the container then solid condensate with irregular impurity distribution is 
forming. Then most pure part of the condensate may be extracted as product. The process may be iterated many 



Distillation 19 

times by moving (without turnover) the received condensate to the bottom part of the container on the place of 
refined matter. The irregular impurity distribution in the condensate (that is efficiency of purification) increases with 
number of repetitions of the process. Zone distillation is a distillation analog of zone recrystallization. Impurity 
distribution in the condensate is described by known equations of zone recrystallization with various numbers of 
iteration of process - with replacement distribution efficient k of crystallization on separation factor a of 
distillation. 

Other types 

• The process of reactive distillation involves using the reaction vessel as the still. In this process, the product is 
usually significantly lower-boiling than its reactants. As the product is formed from the reactants, it is vaporized 
and removed from the reaction mixture. This technique is an example of a continuous vs. a batch process; 
advantages include less downtime to charge the reaction vessel with starting material, and less workup. 

• Catalytic distillation is the process by which the reactants are catalyzed while being distilled to continuously 
separate the products from the reactants. This method is used to assist equilibrium reactions reach completion. 

• Pervaporation is a method for the separation of mixtures of liquids by partial vaporization through a non-porous 
membrane. 

• Extractive distillation is defined as distillation in the presence of a miscible, high boiling, relatively non- volatile 
component, the solvent, that forms no azeotrope with the other components in the mixture. 

• Flash evaporation (or partial evaporation) is the partial vaporization that occurs when a saturated liquid stream 
undergoes a reduction in pressure by passing through a throttling valve or other throttling device. This process is 
one of the simplest unit operations, being equivalent to a distillation with only one equilibrium stage. 

• Codistillation is distillation which is performed on mixtures in which the two compounds are not miscible. 

The unit process of evaporation may also be called "distillation": 

• In rotary evaporation a vacuum distillation apparatus is used to remove bulk solvents from a sample. Typically the 
vacuum is generated by a water aspirator or a membrane pump. 

• In a kugelrohr a short path distillation apparatus is typically used (generally in combination with a (high) vacuum) 
to distill high boiling (> 300 °C) compounds. The apparatus consists of an oven in which the compound to be 
distilled is placed, a receiving portion which is outside of the oven, and a means of rotating the sample. The 
vacuum is normally generated by using a high vacuum pump. 

Other uses: 

• Dry distillation or destructive distillation, despite the name, is not truly distillation, but rather a chemical reaction 
known as pyrolysis in which solid substances are heated in an inert or reducing atmosphere and any volatile 
fractions, containing high-boiling liquids and products of pyrolysis, are collected. The destructive distillation of 
wood to give methanol is the root of its common name - wood alcohol. 

• Freeze distillation is an analogous method of purification using freezing instead of evaporation. It is not truly 
distillation, but a recrystallization where the product is the mother liquor, and does not produce products 
equivalent to distillation. This process is used in the production of ice beer and ice wine to increase ethanol and 
sugar content, respectively. It is also used to produce applejack. Unlike distillation, freeze distillation concentrates 
poisonous congeners rather than removing them; As a result, many countries prohibit such applejack as a health 
measure. However, reducing methanol with the absorption of 4A molecular sieve is a practical method for 
production. Also, distillation by evaporation can separate these since they have different boiling points. 



Distillation 20 

Azeotropic distillation 

Interactions between the components of the solution create properties unique to the solution, as most processes entail 
nonideal mixtures, where Raoult's law does not hold. Such interactions can result in a constant-boiling azeotrope 
which behaves as if it were a pure compound (i.e., boils at a single temperature instead of a range). At an azeotrope, 
the solution contains the given component in the same proportion as the vapor, so that evaporation does not change 
the purity, and distillation does not effect separation. For example, ethyl alcohol and water form an azeotrope of 
95.6% at 78.1 °C. 

If the azeotrope is not considered sufficiently pure for use, there exist some techniques to break the azeotrope to give 
a pure distillate. This set of techniques are known as azeotropic distillation. Some techniques achieve this by 
"jumping" over the azeotropic composition (by adding an additional component to create a new azeotrope, or by 
varying the pressure). Others work by chemically or physically removing or sequestering the impurity. For example, 
to purify ethanol beyond 95%, a drying agent or a (desiccant such as potassium carbonate) can be added to convert 
the soluble water into insoluble water of crystallization. Molecular sieves are often used for this purpose as well. 

Immiscible liquids, such as water and toluene, easily form azeotropes. Commonly, these azeotropes are referred to as 
a low boiling azeotrope because the boiling point of the azeotrope is lower than the boiling point of either pure 
component. The temperature and composition of the azeotrope is easily predicted from the vapor pressure of the pure 
components, without use of Raoult's law. The azeotrope is easily broken in a distillation set-up by using a 
liquid-liquid separator (a decanter) to separate the two liquid layers that are condensed overhead. Only one of the 
two liquid layers is refluxed to the distillation set-up. 

High boiling azeotropes, such as a 20 weight percent mixture of hydrochloric acid in water, also exist. As implied by 
the name, the boiling point of the azeotrope is greater than the boiling point of either pure component. 

To break azeotropic distillations and cross distillation boundaries, such as in the DeRosier Problem, it is necessary to 
increase the composition of the light key in the distillate. 

Breaking an azeotrope with unidirectional pressure manipulation 

The boiling points of components in an azeotrope overlap to form a band. By exposing an azeotrope to a vacuum or 
positive pressure, it's possible to bias the boiling point of one component away from the other by exploiting the 
differing vapour pressure curves of each; the curves may overlap at the azeotropic point, but are unlikely to be 
remain identical further along the pressure axis either side of the azeotropic point. When the bias is great enough, the 
two boiling points no longer overlap and so the azeotropic band disappears. 

This method can remove the need to add other chemicals to a distillation, but it has two potential drawbacks. 

Under negative pressure, power for a vacuum source is needed and the reduced boiling points of the distillates 
requires that the condenser be run cooler to prevent distillate vapours being lost to the vacuum source. Increased 
cooling demands will often require additional energy and possibly new equipment or a change of coolant. 

Alternatively, if positive pressures are required, standard glassware can not be used, energy must be used for 
pressurization and there is a higher chance of side reactions occurring in the distillation, such as decomposition, due 
to the higher temperatures required to effect boiling. 

A unidirectional distillation will rely on a pressure change in one direction, either positive or negative. 



Distillation 



21 



Pressure-swing distillation 

Pressure-swing distillation is essentially the same as the unidirectional distillation used to break azeotropic mixtures, 
but here both positive and negative pressures may be employed. Wikipedia:Please clarify 

This has an important impact on the selectivity of the distillation and allows a chemist ^ ciaion nee e to optimize a 
process such that fewer extremes of pressure and temperature are required and less energy is consumed. This is 
particularly important in commercial applications. 

Pressure-swing distillation is employed during the industrial purification of ethyl acetate after its catalytic synthesis 
from ethanol. 



Industrial distillation 

Large scale industrial distillation applications include both batch and 
continuous fractional, vacuum, azeotropic, extractive, and steam 
distillation. The most widely used industrial applications of 
continuous, steady-state fractional distillation are in petroleum 
refineries, petrochemical and chemical plants and natural gas 
processing plants. 

Industrial distillation is typically performed in large, vertical 
cylindrical columns known as distillation towers or distillation 
columns with diameters ranging from about 65 centimeters to 16 
meters and heights ranging from about 6 meters to 90 meters or more. 
When the process feed has a diverse composition, as in distilling crude 
oil, liquid outlets at intervals up the column allow for the withdrawal of 
different fractions or products having different boiling points or boiling 
ranges. The "lightest" products (those with the lowest boiling point) 
exit from the top of the columns and the "heaviest" products (those 
with the highest boiling point) exit from the bottom of the column and 
are often called the bottoms. 




Typical industrial distillation towers 



Distillation 



22 



Condenser 




"1 Reflux 
- 1 -^Drum 



Pump 
Overhead t 
product 



Bottoms 
liquid 



Steam 
Condensate 

Bottoms 
product 



t Upflowing vapor 
Downflowing liquid 



Industrial towers use reflux to achieve a more complete separation of 
products. Reflux refers to the portion of the condensed overhead liquid 
product from a distillation or fractionation tower that is returned to the 
upper part of the tower as shown in the schematic diagram of a typical, 
large-scale industrial distillation tower. Inside the tower, the 
downflowing reflux liquid provides cooling and condensation of the 
upflowing vapors thereby increasing the efficiency of the distillation 
tower. The more reflux that is provided for a given number of 
theoretical plates, the better the tower's separation of lower boiling 
materials from higher boiling materials. Alternatively, the more reflux 
that is provided for a given desired separation, the fewer the number of 
theoretical plates required. 

Such industrial fractionating towers are also used in air separation, 
producing liquid oxygen, liquid nitrogen, and high purity argon. 
Distillation of chlorosilanes also enables the production of high-purity 
silicon for use as a semiconductor. 



Diagram of a typical industrial distillation tower 



Design and operation of a distillation tower depends on the feed and 
desired products. Given a simple, binary component feed, analytical 
methods such as the McCabe-Thiele method or the Fenske equation u 
can be used. For a multi-component feed, simulation models are used 
both for design and operation. Moreover, the efficiencies of the 
vapor-liquid contact devices (referred to as "plates" or "trays") used in 
distillation towers are typically lower than that of a theoretical 100% 
efficient equilibrium stage. Hence, a distillation tower needs more trays 
than the number of theoretical vapor-liquid equilibrium stages. 



! bubble! ■ 
■: -J. caps. ];.■. 



■■A--- 
. ■:.!'■ ■■ 

;;■.]■ ::" 



Ilk 



bubble 
caps 



' 

$ ■■ 4 ■!■ 4 tray 




pwLn uTiuriuriunuriLt 

I tray + 4 + '+" + +* l 
I . .- Iv Vl-".:,-"" I;- "- |'>- .1 "-.: . "I §^ I 

I I I .1 I I Jill 

I ■ I v ,l a | P | o | r .||^f 



Section of an industrial distillation tower showing 
detail of trays with bubble caps 



In modern industrial uses, a packing material is used in the column 

instead of trays when low pressure drops across the column are 

required. Other factors that favor packing are: vacuum systems, smaller 

diameter columns, corrosive systems, systems prone to foaming, 

systems requiring low liquid holdup and batch distillation. Conversely, factors that favor plate columns are: presence 

of solids in feed, high liquid rates, large column diameters, complex columns, columns with wide feed composition 

variation, columns with a chemical reaction, absorption columns, columns limited by foundation weight tolerance, 

low liquid rate, large turn-down ratio and those processes subject to process surges. 



Distillation 



23 



This packing material can either be random dumped packing (1-3" 
wide) such as Raschig rings or structured sheet metal. Liquids tend to 
wet the surface of the packing and the vapors pass across this wetted 
surface, where mass transfer takes place. Unlike conventional tray 
distillation in which every tray represents a separate point of 
vapor-liquid equilibrium, the vapor-liquid equilibrium curve in a 
packed column is continuous. However, when modeling packed 
columns, it is useful to compute a number of "theoretical stages" to 
denote the separation efficiency of the packed column with respect to 
more traditional trays. Differently shaped packings have different 
surface areas and void space between packings. Both of these factors 
affect packing performance. 

Another factor in addition to the packing shape and surface area that 
affects the performance of random or structured packing is the liquid 
and vapor distribution entering the packed bed. The number of 
theoretical stages required to make a given separation is calculated 
using a specific vapor to liquid ratio. If the liquid and vapor are not 
evenly distributed across the superficial tower area as it enters the 
packed bed, the liquid to vapor ratio will not be correct in the packed 
bed and the required separation will not be achieved. The packing will 
appear to not be working properly. The height equivalent of a 
theoretical plate (HETP) will be greater than expected. The problem is 
not the packing itself but the mal-distribution of the fluids entering the 
packed bed. Liquid mal-distribution is more frequently the problem than vapor. The design of the liquid distributors 
used to introduce the feed and reflux to a packed bed is critical to making the packing perform to it maximum 
efficiency. Methods of evaluating the effectiveness of a liquid distributor to evenly distribute the liquid entering a 
packed bed can be found in references. Considerable work as been done on this topic by Fractionation Research, 




Large-scale, industrial vacuum distillation 

, [17] 
column 



Inc. (commonly known as FRI). 



[] 



Multi-effect distillation 

The goal of multi-effect distillation is to increase the energy efficiency of the process, for use in desalination, or in 
some cases one stage in the production of ultrapure water. The number of effects is proportional to the kW-h/m of 
water recovered figure, and refers to the volume of water recovered per unit of energy compared with single-effect 
distillation. One effect is roughly 636 kWh/m . 

• Multi-stage flash distillation Can achieve more than 20 effects with thermal energy input, as mentioned in the 
article. 

• Vapor compression evaporation Commercial large-scale units can achieve around 72 effects with electrical 
energy input, according to manufacturers. 

There are many other types of multi-effect distillation processes, including one referred to as simply multi-effect 
distillation (MED), in which multiple chambers, with intervening heat exchangers, are employed. 



Distillation 



24 



Distillation in food processing 
Distilled beverages 

Carbohydrate-containing plant materials are allowed to ferment, producing a dilute solution of ethanol in the process. 
Spirits such as whiskey and rum are prepared by distilling these dilute solutions of ethanol. Components other than 
ethanol, including water, esters, and other alcohols, are collected in the condensate, which account for the flavor of 
the beverage. 

Gallery 




>v 



Chemistry in its beginnings used retorts as laboratory equipment exclusively for distillation processes. 




A simple set-up to distill dry and oxygen-free toluene. 





Diagram of an industrial-scale vacuum distillation column as commonly used in oil refineries 



A rotary evaporator is able to distill solvents more quickly at lower temperatures through the use of a vacuum. 



Distillation using semi-microscale apparatus. The jointless design eliminates the need to fit pieces together. The pear-shaped 
flask allows the last drop of residue to be removed, compared with a similarly- sized round-bottom flask The small holdup 
volume prevents losses. A pig is used to channel the various distillates into three receiving flasks. If necessary the distillation 
can be carried out under vacuum using the vacuum adapter at the pig. 



Notes 

[3] Magnum Opus Hermetic Sourceworks Series (http://www.alchemywebsite.com/bookshop/mohs32.html) 

[4] http://www.levity.com/alchemy/jfren_ar.html 

[5] Industrial Engineering Chemistry (1936) page 677 

[6] Sealing Technique (http://www.copper-alembic.com/manufacturing/specs_sealing.php), accessed 16 November 2006. 

[7] Traditional Alembic Pot Still (http://www.essentialoil.com/alembic5.html), accessed 16 November 2006. 

[8] D. F. Othmer (1982) Distillation — Some Steps in its Development, in W. F. Furter (ed) A Century of Chemical Engineering ISBN 

0-306-40895-3 
[9] A. Coffey British Patent 5974, 5 August 1830 
[10] Improvement in the Ammonia-Soda Manufacture 
[11] ST07 Separation of liquid-liquid mixtures (solutions) (http://www.iupac.org/didac/Didac Eng/Didac05/Content/ST07.htm), DID AC 

by IUPAC 
[12] Fractional Distillation (http://wulfenite.fandm.edu/labtech/fractdistill.htm) 
[13] Spinning Band Distillation (http://www.brinstrument.com/fractional-distillation/spinning_band_distillation.html) at B/R Instrument 

Corporation (accessed 8 September 2006) 
[14] Vogel's 5th ed. 

[16] http://124.205.222.100/Jwk_spkx/EN/abstract/abstractl5544.shtml 
[17] Energy Institute website page (http://resources.schoolscience.co.Uk/SPE/knowl/4/2index.htm7vacuum.html) 



Distillation 



25 



[18] Random Packing, Vapor and Liquid Distribution: Liquid and gas distribution in commercial packed towers, Moore, F., Rukovena, F., 
Chemical Plants & Processing, Edition Europe, August 1987, p. 11-15 

Further reading 

• Allchin, F. R. (1979). "India: The Ancient Home of Distillation?". Man 14 (1): 55-63. doi: 10.2307/2801640 
(http://dx.doi.org/10.2307/2801640). JSTOR 2801640 (http://www.jstor.org/stable/2801640). 

• Forbes, R. J. (1970). A Short History of the Art of Distillation from the Beginnings up to the Death of Cellier 
Blumenthal (http: //books. google. com/ ?id=XeqWOkKYn2 8 C&printsec=frontcover). BRILL. 

ISBN 90-04-00617-6. 

• Needham, Joseph (1980). Science and Civilisation in China (http://books.google.com/ 

books ?id=JvLroG7r2MYC&printsec=frontcover). Cambridge University Press. ISBN 0-521-08573-X. 

• Geankoplis, Christie John (2003). Transport Processes and Separation Process Principles (4th ed.). Prentice 
Hall. ISBN 0-13-101367-X. 

External links 

• Alcohol distillation (http://www.agcom.purdue.edu/AgCom/Pubs/AE/AE-117.html) 

• Case Study: Petroleum Distillation (http://www.members.tripod.com/historycheme/h_distill.html) 

• "Binary Vapor-Liquid Equilibrium Data" (http://www.cheric.org/research/kdb/hcvle/hcvle.php) (searchable 
database). Chemical Engineering Research Information Center. Retrieved 5 May 2007. 



Essential oil 




An essential oil is a concentrated hydrophobic liquid containing 
volatile aroma compounds from plants. Essential oils are also known as 
volatile oils, ethereal oils or aetherolea, or simply as the "oil of" the 
plant from which they were extracted, such as oil of clove. An oil is 
"essential" in the sense that it carries a distinctive scent, or essence, of 
the plant. Essential oils do not form a distinctive category for any 
medical, pharmacological, or culinary purpose. 

Essential oils are generally extracted by distillation. Steam distillation 
is often used. Other processes include expression or solvent extraction. 
They are used in perfumes, cosmetics, soaps and other products, for 
flavoring food and drink, and for adding scents to incense and 
household cleaning products. 

Essential oils have been used medicinally in history. Medical 
applications proposed by those who sell medicinal oils range from skin 
treatments to remedies for cancer and often are based solely on 
historical accounts of use of essential oils for these purposes. Claims 
for the efficacy of medical treatments, and treatment of cancers in 

particular, are now subject to regulation in most countries. 

A glass vial containing sandalwood oil 

As the use of essential oils has declined in evidence-based medicine, 

one must consult older textbooks for much information on their 

use. Modern works are less inclined to generalize; rather than refer to "essential oils" as a class at all, they prefer 

to discuss specific compounds, such as methyl salicylate, rather than "oil of wintergreen". 






[][] 



Essential oil 26 

Interest in essential oils has revived in recent decades with the popularity of aromatherapy, a branch of alternative 
medicine that claims that essential oils and other aromatic compounds have curative effects. Oils are volatilized or 
diluted in a carrier oil and used in massage, diffused in the air by a nebulizer, heated over a candle flame, or burned 
as incense. 

The earliest recorded mention of the techniques and methods used to produce essential oils is believed to be that of 
Ibn al-Baitar (1188-1248), an Andalusian physician, pharmacist and chemist. 

Production 

Distillation 

Today, most common essential oils — such as lavender, peppermint, and eucalyptus — are distilled. Raw plant 
material, consisting of the flowers, leaves, wood, bark, roots, seeds, or peel, is put into an alembic (distillation 
apparatus) over water. As the water is heated, the steam passes through the plant material, vaporizing the volatile 
compounds. The vapors flow through a coil, where they condense back to liquid, which is then collected in the 
receiving vessel. 

Most oils are distilled in a single process. One exception is ylang-ylang (Cananga odorata), which takes 22 hours to 
complete through a fractional distillation. 

The recondensed water is referred to as a hydrosol, hydrolat, herbal distillate or plant water essence, which may be 
sold as another fragrant product. Popular hydrosols include rose water, lavender water, lemon balm, clary sage and 
orange blossom water. The use of herbal distillates in cosmetics is increasing. Some plant hydrosols have unpleasant 
smells and are therefore not sold. 

Expression 

Most citrus peel oils are expressed mechanically or cold-pressed (similar to olive oil extraction). Due to the 
relatively large quantities of oil in citrus peel and low cost to grow and harvest the raw materials, citrus-fruit oils are 
cheaper than most other essential oils. Lemon or sweet orange oils that are obtained as byproducts of the citrus 
industry are even cheaper. 

Before the discovery of distillation, all essential oils were extracted by pressing. 

Solvent extraction 

Most flowers contain too little volatile oil to undergo expression; their chemical components are too delicate and 
easily denatured by the high heat used in steam distillation. Instead, a solvent such as hexane or supercritical carbon 
dioxide is used to extract the oils. Extracts from hexane and other hydrophobic solvent are called concretes, which 
are a mixture of essential oil, waxes, resins, and other lipophilic (oil soluble) plant material. 

Although highly fragrant, concretes contain large quantities of nonfragrant waxes and resins. Often, another solvent, 
such as ethyl alcohol, which is more polar in nature, is used to extract the fragrant oil from the concrete. The alcohol 
is removed by evaporation, leaving behind the absolute. 

Supercritical carbon dioxide is used as a solvent in supercritical fluid extraction. This method has many benefits 
including avoiding petrochemical residues in the product and the loss of some "top notes" when steam distillation is 
used. It does not yield an absolute directly. The supercritical carbon dioxide will extract both the waxes and the 
essential oils that make up the concrete. Subsequent processing with liquid carbon dioxide, achieved in the same 
extractor by merely lowering the extraction temperature, will separate the waxes from the essential oils. This lower 
temperature process prevents the decomposition and denaturing of compounds. When the extraction is complete, the 
pressure is reduced to ambient and the carbon dioxide reverts to a gas, leaving no residue. An animated presentation 
describing the process is available for viewing. 



Essential oil 



27 



Supercritical carbon dioxide is also used for making decaffeinated coffee. Although it uses the same basic principles, 
it is a different process because of the difference in scale. 

Florasols extraction 

Florasol (R134a), a refrigerant, was developed to replace Freon. Florasol is an ozone friendly product and it poses 
little danger to the environment. One advantage is that the extraction of essential oils occurs at or below room 
temperature so degradation through high temperature extremes does not occur. The essential oils are mostly pure and 

. • 1..1 . r • i . [citation needed] 

contain little to no foreign substances. 

Production quantities 

Estimates of total production of essential oils are difficult to obtain. One estimate, compiled from data in 1989, 1990 
and 1994 from various sources, gives the following total production, in tonnes, of essential oils for which more than 
1,000 tonnes were produced. 



Oil 


Tonnes 


Sweet orange 


12,000 


Mentha arvensis 


4,800 


Peppermint 


3,200 


Cedarwood 


2,600 


Lemon 


2,300 


Eucalyptus globulus 


2,070 


Litsea cubeba 


2,000 


Clove (leaf) 


2,000 


Spearmint 


1,300 



Pharmacology 



[6] 



Although some are suspicious or dismissive towards the use of essential oils in healthcare or pharmacology 
essential oils retain considerable popular use, partly in fringe medicine and partly in popular remedies. Therefore it is 
difficult to obtain reliable references concerning their pharmacological merits. 

Studies have shown that certain essential oils may have the ability to prevent the transmission of some drug-resistant 
strains of pathogen, specifically Staphylococcus, Streptococcus and Candida. 

Taken by mouth, many essential oils can be dangerous in high concentrations. Typical effects begin with a burning 
feeling, followed by salivation. In the stomach, the effect is carminative, relaxing the gastric sphincter and 
encouraging eructation (belching). Further down the gut, the effect typically is antispasmodic. 

Typical ingredients for such applications include eucalyptus oils, menthol, capsaicin, anise and camphor. Other 
essential oils work well in these applications, but it is notable that others offer no significant benefit. This illustrates 
the fact that different essential oils may have drastically different pharmacology. Those that do work well for upper 
respiratory tract and bronchial problems act variously as mild expectorants and decongestants. Some act as locally 
anaesthetic counterirritants and, thereby, exert an antitussive effect. 

[8] 



Some essential oils, such as those of juniper and agathosma, are valued for their diuretic effects. With relatively 
recent concerns about the overuse of antibacterial agents, many essential oils have seen a resurgence in 
off-label use for such properties and are being examined for this use clinically. 



Essential oil 



28 



Many essential oils affect the skin and mucous membranes in ways that are valuable or harmful. They are used in 
antiseptics and liniments in particular. Typically, they produce rubefacient irritation at first and then counterirritant 
numbness. Turpentine oil and camphor are two typical examples of oils that cause such effects. Menthol and some 
others produce a feeling of cold followed by a sense of burning. This is caused by its effect on heat- sensing nerve 
endings. Some essential oils, such as clove oil or eugenol, were popular for many years in dentistry as antiseptics and 
local anaesthetics. Thymol is well known for its antiseptic effects. 

Use in aromatherapy 

Aromatherapy is a form of alternative medicine in which healing effects are ascribed to the aromatic compounds in 
essential oils and other plant extracts. Many common essential oils have medicinal properties that have been applied 
in folk medicine since ancient times and are still widely used today. For example, many essential oils have antiseptic 
properties. Many are also claimed to have an uplifting effect on the mind. Such claims, if meaningful, are not 
necessarily false but are difficult to quantify in the light of the sheer variability of materials used in the practice. 

Dilution 

Essential oils are usually lipophilic (literally: "oil-loving") compounds that usually are not miscible with water. Also, 
they can be diluted in solvents like pure ethanol, and polyethylene glycol. 

Raw materials 

Essential oils are derived from sections of plants. Some plants, like the bitter orange, are sources of several types of 
essential oil. 



Berries 

• Allspice 

• Juniper 

Seeds 

• Almond 

• Anise 

• Buchu 

• Celery 

• Cumin 

• Nutmeg oil 

Bark 

• Cassia 

• Cinnamon 

• Sassafras 

Wood 

• Camphor 

• Cedar 

• Rosewood 

• Sandalwood 

• Agarwood 

Rhizome 

• Galangal 

• Ginger 


Leaves 

• Basil 

• Bay leaf 

• Buchu 

• Cinnamon 

• Common sage 

• Eucalyptus 

• Guava 

• Lemon grass 

• Melaleuca 

• Oregano 

• Patchouli 

• Peppermint 

• Pine 

• Rosemary 

• Spearmint 

• Tea tree 

• Thyme 

• Tsuga 

• Wintergreen 

Resin 

• Benzoin 

• Copaiba 

• Frankincense 

• Myrrh 


Flowers 

• Cannabis 

• Chamomile 

• Clary sage 

• Clove 

• Scented geranium 

• Hops 

• Hyssop 

• Jasmine 

• Lavender 

• Manuka 

• Marjoram 

• Orange 

• Rose 

• Ylang-ylang 

Peel 

• Bergamot 

• Grapefruit 

• Lemon 

• Lime 

• Orange 

• Tangerine 

Root 

• Valerian 



Essential oil 29 

Eucalyptus oil 

Apart from essential oils used mainly in foods, the best-known essential oil worldwide might be eucalyptus oil, 
produced from the leaves of Eucalyptus globulus. Steam-distilled eucalyptus oil is used throughout Asia, Africa, 
Latin America and South America as a primary cleaning/disinfecting agent added to soaped mop and countertop 
cleaning solutions; it also possesses insect and limited vermin control properties. Note, however, there are hundreds 
of species of eucalyptus, and perhaps some dozens are used to various extents as sources of essential oils. Not only 
do the products of different species differ greatly in characteristics and effects, but also the products of the very same 
tree can vary grossly. 

Rose oil 

The second most well-known essential oil is probably rose oil, produced from the petals of Rosa damascena and 
Rosa centifolia. Steam-distilled rose oil is known as "rose otto", while the solvent extracted product is known as 
"rose absolute". 

Lavender essential oil 

One of the most popular essential oils in the world, lavender essential oil has a reputation of being mild, relaxing and 

• . n 11 i i T i .. i -i • i . . 11 . [citation needed] 

appropriate for all ages and genders. Lavender essential oil is also an insect repellant. 

Dangers 

The potential danger of an essential oil is generally relative to its level or grade of purity. Many essential oils are 
designed exclusively for their aroma- therapeutic quality; these essential oils generally should not be applied directly 
to the skin in their undiluted or "neat" form. Some can cause severe irritation, provoke an allergic reaction and, over 
time, prove hepatotoxic. Non-therapeutic grade essential oils are never recommended for topical or internal use. 

Essential oils should not be used with animals, as they possess extreme hepatotoxicity and dermal toxicity for 
animals, especially for cats. Instead, essential oils should be blended with a vegetable-based carrier oil (as a base, or 
"fixed" oil) before being applied. Common carrier oils include olive, almond, hazelnut and grapeseed. Only neutral 
oils should be used. A common ratio of essential oil disbursed in a carrier oil is 0.5%— 3% (most under 10%), 
depending on its purpose. Some essential oils, including many of the citrus peel oils, are photosensitizers, increasing 
the skin's vulnerability to sunlight. 

Industrial users of essential oils should consult the material safety data sheets (MSDS) to determine the hazards and 
handling requirements of particular oils. Even certain therapeutic grade oils can pose potential threats to individuals 
with epilepsy or pregnant women. 

Handling 

Essential oils can be aggressive toward rubbers and plastics, so care must be taken in choosing the correct handling 
equipment. Glass syringes are often used, but have coarse volumetric graduations. Chemistry syringes are ideal, as 
they resist essential oils, are long enough to enter deep vessels, and have fine graduations, facilitating quality control. 
Unlike traditional pipettes, which have difficulty handling viscous fluids, the chemistry syringe has a seal and piston 
arrangement which slides inside the pipette, wiping the essential oil off the pipette wall. This improves accuracy, and 
the inside of the pipette is easy to clean and reuse immediately. Chemistry pipetting syringes are equal in accuracy to 
the best laboratory equipment and are available in sizes from 1 mL through 25 mL. 



Essential oil 



30 



Pregnancy 

The use of essential oils in pregnancy is not recommended due to inadequate published evidence to demonstrate 
evidence of safety. nee e Pregnant women often report an abnormal sensitivity to smells and taste, 

essential oils can cause irritation and nausea. 

Gynecomastia 

Estrogenic and antiandrogenic activity have been reported by in vitro study of tea tree oil and lavender essential oils. 
Case reports suggest the oils may be implicated in some cases of gynecomastia, an abnormal breast tissue growth, in 
prepubescent boys. 

Pesticide residues 

There is some concern about pesticide residues in essential oils, particularly those used therapeutically. For this 
reason, many practitioners of aromatherapy buy organically produced oils. nee e Not only are pesticides 

present in trace quantities, but also the oils themselves are used in tiny quantities and usually in high dilutions. 
Where there is a concern about pesticide residues in food essential oils, such as mint or orange oils, the proper 
criterion is not whether the material is alleged to be organically produced, but whether it meets the government 
standards based on actual analysis of its pesticide content. 

Ingestion 

Essential oils are used extensively as GRAS flavoring agents in foods, beverages and confectioneries according to 
strict Good Manufacturing Practice (GMP) and flavorist standards. Therapeutic grade essential oils are generally safe 

for human consumption in small amounts. Pharmacopoeia standards for medicinal oils should be heeded. Some oils 

ri7i 
can be toxic to some domestic animals, cats in particular. 1 The internal use of essential oils can pose hazards to 

pregnant women, as some can be abortifacients in dose 0.5-10 ml, and thus should not be used during pregnancy. 

Flammability 

The flash point of each essential oil is different. Many of the common essential oils, such as tea tree, lavender, and 
citrus oils, are classed as a Class 3 Flammable Liquid, as they have a flash point of 50-60 °C. 



Toxicology 

The following table lists the LD or median lethal dose for common oils; this is the dose required to kill half the 
members of a tested population.LD is intended as a guideline only, and reported values can vary widely due to 



risi 
differences in tested species and testing conditions. 



Common Name 


Oral LD 5Q 


Dermal LD 


Notes 


Neem 


14g/kg 


>2 g/kg 




Lemon myrtle 


2.43 g/kg 


2.25 g/kg 




Frankincense 


>5g/kg 


>5g/kg 


Boswellia carterii 


Frankincense 


>2g/kg 


>2 g/kg 


Boswellia sacra 


Indian frankincense 


>2g/kg 


>2 g/kg 


Boswellia serrata 


Ylang-ylang 


>5g/kg 


>5g/kg 




Cedarwood 


>5g/kg 


>5g/kg 




Roman chamomile 


>5g/kg 


>5g/kg 




White camphor 


>5g/kg 


>5g/kg 


Cinnamomum camphora, extracted from leaves 



Essential oil 



31 



Yellow camphor 


3.73 g/kg 


>5 g/kg 


Cinnamomum camphora, extracted from bark 


Hot oil 


3.80 g/kg 


>5 g/kg 


Cinnamomum camphora, oil extracted from leaves 


Cassia 


2.80 g/kg 


0.32 g/kg 





It is important to understand that the foregoing figures are far less relevant in everyday life than far smaller, often 
localized levels of exposure. For example, a dose of many an essential oil that would do no harm if swallowed in 
diluted solution or emulsion, could do serious damage to eyes or lungs in a higher concentration. 



Standardization of its derived products 

In 2002, ISO published ISO 4720 in which the botanical names of the relevant plants are standardized. The rest of 



the standards with regards to this topic can be found in the section of ICS 71.100.60 



[] 



Notes 

[1] Sapeika, Norman. Actions and uses of Drugs, Pub: A. A. Balkema, 1963 

[2] Thorpe's Dictionary of Applied Chemistry, vol. 8, 4th ed. Pub: Longmans Green. 1947 

[3] E.J. Brill's first encyclopaedia of ... - Google Books (http://books.google.com.pk/books ?id=7CP7fYghB FQC&pg=PA101 1& 

lpg=PA1011&dq=Al-Djildaki&source=bl&ots=F5JrnpOC95&sig=fCHcNXLa0o0nZ189ccurjM9vL8Y&hl=en& 

ei=w2DmS7buNZSPOJq-6NsN&sa=X&oi=book_result&ct=result&resnum=l&ved=0CBUQ6AEwAA#v=onepage&q=Al-Djildaki& 

f=false) 
[4] http://appliedseparations.com/ASInteractive/Overviews/SCF/Essential_Oils/player.html 
[5] It is unclear from the source what period of time the quoted figures include. 
[6] "The healing power of essential oils is the main attraction in aromatherapy. It is also the main question for the skeptic." From " 

Aromoatherapy (http://skepdic.com/aroma.html)" page of Skeptic's Dictionary, accessed 06 Feb 2013 
[7] Haneke, Karen E: Turpentine [8006-64-2] Review of Toxicological Literature Pub.: National Institute of Environmental Health Sciences 

2002 http ://ntp . niehs . nih.gov/ntp/htdocs/Chem_B ackground/ExSumPdf/Turpentine. pdf 
[8] Watt, John Mitchell, Breyer-Brandwijk, Maria Gerdina: The Medicinal and Poisonous Plants of Southern and Eastern Africa 2nd ed Pub. E & 

S Livingstone 1962 
[9] Antibacterial Household Products: Cause for Concern (http://www.cdc.gov/ncidod/eid/vol7no3_supp/levy.htm) 
[10] Essential Oils: Mother Nature's Antibiotics and Disinfectants (http://www.greatestherbsonearth.com/articles/essential_oils.htm) 
[16] For example: Menary,R.C. Minimising pesticide residues in essential oils, 2008 Rural Industries Research and Development Corporation 
[18] http://www.zenitech.com/documents/Toxicity_of_essential_oils_pl.pdf 

References 

• Kurt Schnaubelt (1999). Advanced Aromatherapy: The Science of Essential Oil Therapy. Healing Arts Press. 
ISBN 0-89281-743-7. 

• Wanda Sellar (2001). The Directory of Essential Oils (Reprint ed.). Essex: The C.W. Daniel Company, Ltd. 
ISBN 0-85207-346-1. 

• Robert Tisserand (1995). Essential Oil Safety: A Guide for Health Care Professionals. Churchill Livingstone. 
ISBN 0-443-05260-3. 

• K.H.C. Baser and G. Buchbauer (2010). Handbook of Essential Oils: Science, Technology and Applications. CRC 
Press, Boca Raton, London, New York. ISBN 978-1-4200-6315-8. 



External links 

^ Media related to Essential oils at Wikimedia Commons 



Hash oil 



32 



Hash oil 



Hash oil (also known as honey oil, dabs, shatter, or earwax) is a resinous 
matrix of cannabinoids obtained from the cannabis plant by solvent 
extraction. 

Hash oil is the most potent of three main cannabis products, which are herb 
(marijuana), resin (hashish), and oil (hash oil). 



THC contents 

Reported THC contents vary between sources. The 2009 World Drug Reports 
reports THC content as "may exceed 60%". A 2013 American forensic 
science book gave a range of 10-30% delta-9 THC by weight, and a 1972 
American forensic journal reported a range of 20-65%. 

Usage 

Hash oil can be consumed in various ways, including smoking, vaporization, 
or orally. 



Manufacturing 

Hash oil is a cannabis product obtained from separating resins from leaves by 
solvent extraction. 




Closeup image of a drop of hash oil on 

the end of a needle. 



Cannabis is boiled in a solvent to form a viscous liquid which is then strained 
and the solvent is evaporated to yield hash oil. Flammable solvents used in 
extraction makes the process dangerous. J 

Newer methods like C02 extraction provide a safer way to extract the resin. C02 extraction is a method of using 
high pressure to force a solvent through plant matter. The solvent used for extraction is carbon dioxide. The solvent 
is pushed through the plant matter at a high pressure and separates the cannabinoid resins and terpenes from the plant 
matter. The result is pure, transparent, amber oil. Carbon Dioxide is a natural product which leaves behind no 
residues. C02's purity is its biggest advantage over all other solvents used for plant extraction. Currently, a popular 
extraction solvent is butane which can potentially leave heavy metals behind in the extracted product. 



Social concerns 

Explosion and fire incidents related to manufacturing attempts in homes have been reported. Associated Press 
reports that such incidents in United States have primarily been in west coast states that permit medical marijuana. 

Legality 

Cannabis extracts (including hash oil) are classified as narcotic drugs under Schedule I and IV of the 1961 United 
Nations Single Convention on Narcotic Drugs. 



Statistics 

The 2006 World Drug Report reports that cannabis oil seizures doubled in 2004, and that it represented 0.01% of 

T71 T81 

global cannabis seized. In 2007, 418 kg equivalent of hash oil was seized globally. 



Hash oil 



33 



Australia 

In the Northern Territory, adults found in possession of up to one gram of hash oil can face a fine of up to $200, 
which if paid within 28 days, negates a criminal charge. 

Under New Zealand law hashish, hash oil, THC, and any other preparations containing THC made by processing the 
plant are scheduled as Class B substances. 

Italy 

issues a warning to those in possession of a substance for personal use which contains up to one gram of THC, with 
further sanctions following if the subject re-offends. 

Portugal 

Although provision of tools utilized in production and consumption of cannabis is illegal in Portugal; Portuguese law 
allows for the possession of up to 2.5 grams of hash oil for personal use. 

United States 

The production or possession of hash is illegal in many US states without medical marijuana. States such as Texas as 
well as others consider hash as a controlled substance and is a felony offense. Until guidelines were amended in 
November 1995, Federal law did not explicitly define the difference between marijuana, hash, and hash oil, which 
led to cannabis preparations being assessed case-by-case. Under the new federal guidelines, hashish oil is 
characterized as: 



A preperation of the soluble cannabinioids derived from Cannabis that includes (i) one or more of the 
tetrahydrocannibinols.. ..and (ii) at least two of the following: cannabinol, cannabidiol, or 
cannibichromene, and (iii) is essentially free of plant material. 



United Kingdom 

Hashish is classified as a Class B controlled substance under the Misuse of Drugs Act 1971. The status of "liquid 

ri2i 

cannabis" is "currently the subject of legal argument" The Misuse of Drugs Act: A Guide For Forensic Scientists 
published by the Royal Society of Chemistry suggests that the term "liquid cannabis" is preferable to "hash oil", as it 
does not involve definition of what exactly constitutes an "oil". The authors also recommend adoption of "purified 
form" instead of "solvent extract" when describing hash oil, as the former would not require proof of solvent usage 
by forensic scientists. 



Images 




Hash oil 



40fc 



Hash oil 





Golden cannabis oil 



Full extract oil in oral syringe 



Hash oil 34 

References 

[1] http://www.theatlanticwire.com/national/2013/05/amateurs-guide-dabs/65266/ 



Further reading 

• Gold, D. (1993). Cannabis Alchemy. ISBN 0914171402. 

Liquid-liquid extraction 



Liquid-liquid extraction, also known as solvent extraction and partitioning, is a method to separate compounds 
based on their relative solubilities in two different immiscible liquids, usually water and an organic solvent. It is an 
extraction of a substance from one liquid into another liquid phase. Liquid-liquid extraction is a basic technique in 
chemical laboratories, where it is performed using a separatory funnel. This type of process is commonly performed 
after a chemical reaction as part of the work-up. 

The term partitioning is commonly used to refer to the underlying chemical and physical processes involved in 
liquid— liquid extraction but may be fully synonymous. The term solvent extraction can also refer to the separation of 
a substance from a mixture by preferentially dissolving that substance in a suitable solvent. In that case, a soluble 
compound is separated from an insoluble compound or a complex matrix. 

Solvent extraction is used in nuclear reprocessing, ore processing, the production of fine organic compounds, the 
processing of perfumes, the production of vegetable oils and biodiesel, and other industries. 

Liquid-liquid extraction is possible in non-aqueous systems: In a system consisting of a molten metal in contact with 
molten salts, metals can be extracted from one phase to the other. This is related to a mercury electrode where a 
metal can be reduced, the metal will often then dissolve in the mercury to form an amalgam that modifies its 
electrochemistry greatly. For example, it is possible for sodium cations to be reduced at a mercury cathode to form 
sodium amalgam, while at an inert electrode (such as platinum) the sodium cations are not reduced. Instead, water is 
reduced to hydrogen. A detergent or fine solid can be used to stabilize an emulsion, or third phase. 

Measures of effectiveness 
Distribution ratio 

In solvent extraction, a distribution ratio is often quoted as a measure of how well-extracted a species is. The 
distribution ratio (D) is equal to the concentration of a solute in the organic phase divided by its concentration in the 
aqueous phase. Depending on the system, the distribution ratio can be a function of temperature, the concentration of 
chemical species in the system, and a large number of other parameters. 

Note that D is related to the AG of the extraction process. 

Sometimes, the distribution ratio is referred to as the partition coefficient, which is often expressed as the logarithm. 
Note that a distribution ratio for uranium and neptunium between two inorganic solids (zirconolite and perovskite) 
has been reported. In solvent extraction, two immiscible liquids are shaken together. The more polar solutes 
dissolve preferentially in the more polar solvent, and the less polar solutes in the less polar solvent. In this 
experiment, the nonpolar halogens preferentially dissolve in the nonpolar mineral oil. 



Liquidliquid extraction 



35 



Separation factors 

The separation factor is one distribution ratio divided by another; it is a measure of the ability of the system to 
separate two solutes. For instance, if the distribution ratio for nickel (D ) is 10 and the distribution ratio for silver 

(D A ) is 100, then the silver/nickel separation factor (SF A #XT .) is equal to D A /D . = SF A #XT . = 10. 

v Ag 7 r v Ag/Nr n Ag Ni Ag/Ni 

Decontamination factor 

This is used to express the ability of a process to remove a contaminant from a product. For instance, if a process is 
fed with a mixture of 1:9 cadmium to indium, and the product is a 1:99 mixture of cadmium and indium, then the 
decontamination factor (for the removal of cadmium) of the process is 0.1 / 0.01 = 10. 

Slopes of graphs 

The easy way to work out the extraction mechanism is to draw graphs and measure the slopes. If for an extraction 
system the D value is proportional to the square of the concentration of a reagent (Z) then the slope of the graph of 
log 10 (£>) against log 1Q ([[Z]]) will be two. 

Techniques 

Batchwise single stage extractions 

This is commonly used on the small scale in chemical labs. It is normal to use a separating funnel. For instance, if a 
chemist were to extract anisole from a mixture of water and 5% acetic acid using ether, then the anisole will enter the 
organic phase. The two phases would then be separated. 

The acetic acid can then be scrubbed (removed) from the organic phase by shaking the organic extract with sodium 
bicarbonate. The acetic acid reacts with the sodium bicarbonate to form sodium acetate, carbon dioxide, and water. 



Multistage countercurrent continuous processes 

These are commonly used in industry for the processing of metals such 
as the lanthanides; because the separation factors between the 
lanthanides are so small many extraction stages are needed. In the 
multistage processes, the aqueous raffinate from one extraction unit is 
fed to the next unit as the aqueous feed, while the organic phase is 
moved in the opposite direction. Hence, in this way, even if the 
separation between two metals in each stage is small, the overall 
system can have a higher decontamination factor. 

Multistage countercurrent arrays have been used for the separation of 
lanthanides. For the design of a good process, the distribution ratio 
should be not too high (>100) or too low (<0.1) in the extraction 
portion of the process. It is often the case that the process will have a 
section for scrubbing unwanted metals from the organic phase, and 
finally a stripping section to obtain the metal back from the organic 
phase. 




Multistage Podbielniak contactor centrifuges produce three to five 

stages of theoretical extraction in a single countercurrent pass, and are used in fermentation-based pharmaceutical 

and food additive production facilities. 



Liquidliquid extraction 36 

Centrifugal extractors mix and separate in one unit. Two liquids will be intensively mixed between the spinning rotor 
and the stationary housing at speeds up to 6000 RPM. This develops great surfaces for an ideal mass transfer from 
the aqueous phase into the organic phase. At 200 - 2000 g both phases will be separated again. Centrifugal 
extractors minimize the solvent in the process, optimize the product load in the solvent and extract the aqueous phase 
completely. Counter current and cross current extractions are easily established. 

Extraction without chemical change 

Some solutes such as noble gases can be extracted from one phase to another without the need for a chemical 
reaction (see absorption). This is the simplest type of solvent extraction. When a solvent is extracted, two immiscible 
liquids are shaken together. The more polar solutes dissolve preferentially in the more polar solvent, and the less 
polar solutes in the less polar solvent. Some solutes that do not at first sight appear to undergo a reaction during the 
extraction process do not have distribution ratio that is independent of concentration. A classic example is the 
extraction of carboxylic acids (HA) into nonpolar media such as benzene. Here, it is often the case that the 
carboxylic acid will form a dimer in the organic layer so the distribution ratio will change as a function of the acid 

concentration (measured in either phase). 

2 
For this case, the extraction constant k is described by k = '"HA'"<sub>organic</sub> /'"HA'"<sub>aqueous</sub> 

Solvation mechanism 

Using solvent extraction it is possible to extract uranium, plutonium, or thorium from acid solutions. One solvent 
used for this purpose is the organophosphate tri-n-butyl phosphate. The PUREX process that is commonly used in 
nuclear reprocessing uses a mixture of tri-n-butyl phosphate and an inert hydrocarbon (kerosene), the uranium(VI) 
are extracted from strong nitric acid and are back-extracted (stripped) using weak nitric acid. An organic soluble 
uranium complex [UO (TBP) (NO ) ] is formed, then the organic layer bearing the uranium is brought into contact 
with a dilute nitric acid solution; the equilibrium is shifted away from the organic soluble uranium complex and 
towards the free TBP and uranyl nitrate in dilute nitric acid. The plutonium(IV) forms a similar complex to the 
uranium(VI), but it is possible to strip the plutonium in more than one way; a reducing agent that converts the 
plutonium to the trivalent oxidation state can be added. This oxidation state does not form a stable complex with 
TBP and nitrate unless the nitrate concentration is very high (circa 10 mol/L nitrate is required in the aqueous phase). 
Another method is to simply use dilute nitric acid as a stripping agent for the plutonium. This PUREX chemistry is a 
classic example of a solvation extraction. 

Here in this case D u = k TBP 2 NO<sub>3</sub> 2 

Ion exchange mechanism 

Another extraction mechanism is known as the ion exchange mechanism. Here, when an ion is transferred from the 
aqueous phase to the organic phase, another ion is transferred in the other direction to maintain the charge balance. 
This additional ion is often a hydrogen ion; for ion exchange mechanisms, the distribution ratio is often a function of 
pH. An example of an ion exchange extraction would be the extraction of americium by a combination of terpyridine 
and a carboxylic acid in tert-butyl benzene. In this case 

1 3-3 

D =k terpyridine carboxylic acid H+ 

Another example is the extraction of zinc, cadmium, or lead by a dialkyl phosphinic acid (RPOH) into a nonpolar 
diluent such as an alkane. A non-polar diluent favours the formation of uncharged non-polar metal complexes. 

Some extraction systems are able to extract metals by both the solvation and ion exchange mechanisms; an example 
of such a system is the americium (and lanthanide) extraction from nitric acid by a combination of 
6,6'-/?/ l s , -(5,6-dipentyl-l,2,4-triazin-3-yl)-2,2'-bipyridine and 2-bromohexanoic acid in tert-butyl benzene. At both 
high- and low-nitric acid concentrations, the metal distribution ratio is higher than it is for an intermediate nitric acid 



Liquidliquid extraction 37 

concentration. 

Ion pair extraction 

It is possible by careful choice of counterion to extract a metal. For instance, if the nitrate concentration is high, it is 
possible to extract americium as an anionic nitrate complex if the mixture contains a lipophilic quaternary 
ammonium salt. 

An example that is more likely to be encountered by the 'average ' chemist is the use of a phase transfer catalyst. This 
is a charged species that transfers another ion to the organic phase. The ion reacts and then forms another ion, which 
is then transferred back to the aqueous phase. 

-1 T21 

For instance, the 31.1 kJ mol is required to transfer an acetate anion into nitrobenzene, while the energy required 

-1 T31 
to transfer a chloride anion from an aqueous phase to nitrobenzene is 43.8 kJ mol . Hence, if the aqueous phase 

in a reaction is a solution of sodium acetate while the organic phase is a nitrobenzene solution of benzyl chloride, 

then, when a phase transfer catalyst, the acetate anions can be transferred from the aqueous layer where they react 

with the benzyl chloride to form benzyl acetate and a chloride anion. The chloride anion is then transferred to the 

aqueous phase. The transfer energies of the anions contribute to that given out by the reaction. 

A 43.8 to 31.1 kJ mol - = 12.7 kJ mol - of additional energy is given out by the reaction when compared with 
energy if the reaction had been done in nitrobenzene using one equivalent weight of a tetraalkylammonium acetate. 

Aqueous two-phase extraction 

Aqueous two-phase extraction, also known as two-phase liquid extraction, is a unique form of solvent extraction. In 
an aqueous two-phase extraction, compounds are still separated based on their solubility, but the two immiscible 
phases are both water-based, an aqueous two phase system. 

Aqueous two-phase extractions can have a number of advantages over traditional solvent extraction. Solvents are 
often destructive to proteins, making the traditional extraction impossible for purifying proteins. In addition, organic 
solvents can be flammable, and their use can cause both environmental and health concerns. Aqueous-two phase 
extractions do not require solvents, and so avoid these concerns. 

Types of aqueous two-phase extractions 

Polymer-polymer systems 

In a Polymer-polymer system, both phases are generated by a dissolved polymer. The heavy phase will generally be 
Polyethylene glycol (PEG), and the light phase is generally a polysaccharide. Traditionally, the polymer used is 
dextran. However, dextran is relatively expensive, and research has been exploring using less expensive 
polysaccharides to generate the light phase. 

If the target compound being separated is a protein or enzyme, it is possible to incorporate a ligand to the target into 
one of the polymer phases. This improves the target's affinity to that phase, and improves its ability to partition from 
one phase into the other. This, as well as the absence of solvents or other denaturing agents, makes polymer-polymer 
extractions an attractive option for purifying proteins. 

The two phases of a polymer-polymer system often have very similar densities, and very low surface tension 
between them. Because of this, demixing a polymer— polymer system is often much more difficult than demixing a 
solvent extraction. Methods to improve the demixing include centrifugation, and application of an electric field. 



Liquidliquid extraction 38 

Polymer-salt systems 

Aqueous two-phase systems can also be generated by introducing a high concentration of salt to a polymer solution. 
The polymer phase used is generally still PEG. Generally, a kosmotropic salt, such as Na PO is used, however 
PEG-NaCl systems have been documented when the salt concentration is high enough. 

Since polymer-salt systems demix readily they are easier to use. However, at high salt concentrations, proteins 
generally either denature, or precipitate from solution. Thus, polymer-salt systems are not as useful for purifying 
proteins. 

Ionic liquids 

Ionic liquids are ionic compounds with low melting points. While they are not technically aqueous, recent research 
has experimented with using them in an extraction that does not use organic solvents. 

Applications 

• DNA purification: The ability to purify DNA from a sample is important for many modern biotechnology 
processes. However, samples often contain nucleases that degrade the target DNA before it can be purified. It has 
been shown that DNA fragments will partition into the light phase of a polymer-salt separation system. If ligands 
known to bind and deactivate nucleases are incorporated into the polymer phase, the nucleases will then partition 
into the heavy phase and be deactivated. Thus, this polymer— salt system is a useful tool for purifying DNA from a 
sample while simultaneously protecting it from nucleases. 

• Food Industry: The PEG-NaCl system has been shown to be effective at partitioning small molecules, such as 
peptides and nucleic acids. These compounds are often flavorants or odorants. The system could then be used by 
the food industry to isolate or eliminate particular flavors. 

Kinetics of extraction 

It is important to investigate the rate at which the solute is transferred between the two phases, in some cases by an 
alteration of the contact time it is possible to alter the selectivity of the extraction. For instance, the extraction of 
palladium or nickel can be very slow because the rate of ligand exchange at these metal centers is much lower than 
the rates for iron or silver complexes. 

Aqueous complexing agents 

If a complexing agent is present in the aqueous phase then it can lower the distribution ratio. For instance, in the case 
of iodine being distributed between water and an inert organic solvent such as carbon tetrachloride then the presence 
of iodide in the aqueous phase can alter the extraction chemistry. 

Instead of Z? T +2 being a constant it becomes Z} T +2 = H<sub>2</sub>.<sub>Organic</sub>/[L. A 1 

10 L ° 2 Aqueous 

I<sup>-</sup>.<sub>Aqueous</sub> 

This is because the iodine reacts with the iodide to form I ". The I " anion is an example of a polyhalide anion that is 
quite common. 



Liquidliquid extraction 39 

Industrial process design 

In a typical scenario, an industrial process will use an extraction step in which solutes are transferred from the 
aqueous phase to the organic phase; this is often followed by a scrubbing stage in which unwanted solutes are 
removed from the organic phase, then a stripping stage in which the wanted solutes are removed from the organic 
phase. The organic phase may then be treated to make it ready for use again. 

After use, the organic phase may be subjected to a cleaning step to remove any degradation products; for instance, in 
PUREX plants, the used organic phase is washed with sodium carbonate solution to remove any dibutyl hydrogen 
phosphate or butyl dihydrogen phosphate that might be present. 

Equipment 

Two layers separating during a liquid-liquid extraction. 

While solvent extraction is often done on a small scale by synthetic lab chemists using a separatory funnel or Craig 
apparatus, it is normally done on the industrial scale using machines that bring the two liquid phases into contact 
with each other. Such machines include centrifugal contactors, Thin Layer Extraction, spray columns, pulsed 
columns, and mixer-settlers. 

Extraction of metals 

The extraction methods for a range of metals include: 

• Cobalt - The extraction of cobalt from hydrochloric acid using alamine 336 in meta-xylene} Cobalt can be 
extracted also using Cyanex 272 {Z?/,s , -(2,4,4-trimethylpentyl) phosphinic acid}. 

• Copper - Copper can be extracted using hydroxy oximes as extractants, a recent paper describes an extractant that 
has a good selectivity for copper over cobalt and nickel. 

• Neodymium - This rare earth is extracted by di(2-ethyl-hexyl)phosphoric acid into hexane by an ion exchange 
mechanism. 

• Nickel - Nickel can be extracted using di(2-ethyl-hexyl)phosphoric acid and tributyl phosphate in a hydrocarbon 
diluent (Shellsol). [8] 

• Palladium and platinum - Dialkyl sulfides, tributyl phosphate and alkyl amines have been used for extracting 
these metals. [9][10] 

• Zinc and cadmium - The zinc and cadmium are both extracted by an ion exchange process, the 
A/,A/, J /V / ,A^ / -tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) acts as a masking agent for the zinc and an 
extractant for the cadmium. In the modified Zincex process, zinc is separated from most divalent ions by 
solvent extraction. D2EHPA (Di (2) ethyl hexyl phosphoric acid) is used for this. A zinc ion replaces the proton 
from two D2EHPA molecules. To strip the zinc from the D2EHPA, sulfuric acid is used, at a concentration of 
above 170g/l (typically 240-265g/l). 



Liquidliquid extraction 



40 



References 

• Sikdar, Cole, et al. Aqueous Two-Phase Extractions in Bioseparations: An Assessment. Biotechnology 9:254. 
1991 

• Szlag, Giuliano. A Low-Cost Aqueous Two Phase System for Enzyme Extraction. Biotechnology Techniques 
2:4:277. 1988 

• Dreyer, Kragl. Ionic Liquids for Aqueous Two-Phase Extraction and Stabilization of Enzymes. Biotechnology 
and Bioengineering. 99:6:1416. 2008 

• Boland. Aqueous Two-Phase Systems: Methods and Protocols. Pg 259-269 

• http ://ull. chemistry .uakron. edu/chemsep/extraction/ 

[1] http://www-ssrl.slac.stanford.edu/pubs/activity_rep/ar98/2370-vance.pdf 

[5] M. Filiz, N.A. Sayar and A.A. Sayar, Hydrometallurgy, 2006, 81, 167-173. 

[6] Yoshinari Baba, Minako Iwakuma and Hideto Nagami, Ind. Eng. Chem. Res, 2002, 41, 5835-5841. 

[7] J. M. Sanchez, M. Hidalgo, M. Valiente and V. Salvado, Solvent Extraction and Ion Exchange, 1999, 17, 455-474. 

[10] P. Giridhar, K.A. Venkatesan, T.G. Srinivasan and P.R. Vasudeva Rao, Hydrometallurgy, 2006, 81, 30-39. 



Medical cannabis 



Medical cannabis refers to the parts of the herb cannabis used as a 
physician-recommended form of medicine or herbal therapy, or to 
synthetic forms of specific cannabinoids such as THC 
(delta-9-tetrahydrocannabinol) as a physician-recommended form of 
medicine. The Cannabis plant has a long history of use as medicine, 
with legendary evidence dating back to the Emperor Shen Nung in 
2737 BCE. Cannabis is one of the 50 "fundamental" herbs of 
traditional Chinese medicine, and is prescribed for a broad range of 
indications. 




American Cannabis indica purchased at a 
medical cannabis dispensary. 



Medical cannabis 



41 




FLUIDEXTRACT 

CANNABIS INDICA 







^ican Dmggists^ Sv*at* 



Cannabis indica fluid extract, American 
Druggists Syndicate, pre- 1937. 



Difference between C. indica and C. sariva 

Cannabis indica has a higher level of CBD compared to THC, while 

Cannabis sativa has a higher level of THC compared to CBD. 

Cannabis strains with relatively high CBD:THC ratios are less likely to 

induce anxiety than vice versa. This may be due to CBD's antagonistic 

effects at the cannabinoid receptors, compared to THC's partial agonist 

effect. CBD is also a 5-HT receptor agonist, which may also 

contribute to an anxiolytic effect. This likely means the high 

concentrations of CBD found in Cannabis indica mitigate the 

anxiogenic effect of THC significantly. The effects of sativa are well 

known for its cerebral high, hence used daytime as medical cannabis, 

while indica is well known for its sedative effects and preferred night 

time as medical cannabis. The plant Cannabis sativa is known to 

cause more of a "high" by stimulating hunger and by producing a 

rather more comedic, or energetic feeling. Conversely, the Cannabis 

indica plant is known to cause more of a "stoned" or meditative 

Hi 
feeling, possibly because of a higher CBD to THC ratio. The primary 

effects of sativas are on the mind and emotions. These benefits can be 




Cannabis sativa, Cannabis indica, and Cannabis 
ruderalis 



Medical cannabis 



42 



particularly helpful for the psychological aspects of many illnesses, giving people an increased sense of well-being. 
Due to the stimulating nature of sativas, they are generally better for daytime use. Caution should also be taken for 
people experiencing heightened anxiety or those with mental health conditions, 
contradicted by more recent research which suggests that CBD increases alertness. 



[3] 



However, this association is 




Use 

Medical cannabis is illegal in most countries. A number of 
governments, including the U.S. Federal Government, allow treatment 
with one or more specific low doses of synthetic cannabinoids for one 
or more disorders. However, public opinion in several areas, including 
the United States, is swinging in favor of use of medical cannabis, 
especially for chronically ill patients. The topic is one of great 
controversy and is being debated more than ever. 

Studies have shown cannabis does have several well-documented 
beneficial effects. Among these are: the amelioration of nausea 

and vomiting, stimulation of hunger in chemotherapy and AIDS 
patients, lowered intraocular eye pressure (shown to be effective for 
treating glaucoma), as well as gastrointestinal illness. It also has 
antibacterial effects and is one of the best known expectorants. 

There are several methods for administration of dosage, including 
vaporizing or smoking dried buds, drinking, or eating extracts, and 
taking capsules. The comparable efficacy of these methods was the 
subject of an investigative study conducted by the National Institutes of Health. 

Synthetic cannabinoids are available as prescription drugs in some countries. Examples are Marinol (The United 
States and Canada) and Cesamet (Canada, Mexico, the United Kingdom, and the United States). 

While utilizing cannabis for recreational purposes is illegal in many parts of the world, many countries are beginning 
to entertain varying levels of decriminalization for medical usage, including Canada, Austria, Germany, Switzerland, 
the Netherlands, Czech Republic, Spain, Israel, Italy, Finland, and Portugal. In the United States, federal law outlaws 
all use of herb parts from Cannabis; States that have approved use of medical cannabis are in conflict with federal 
law. The United States Supreme Court has ruled in United States v. Oakland Cannabis Buyers' Coop and Gonzales v. 
Raich that the federal government has a right to regulate and criminalize cannabis, even for medical purposes. A 
person can therefore be prosecuted for a cannabis-related crime even if it is legal medical use according to state laws. 
The US federal government, through the National Institute on Drug Abuse (NIDA), continues to provide medical 
cannnabis to 4 patients who participated in the Compassionate Investigational New Drug Program. 1 NIDA claims 
this is done for "compassionate purposes" and the US federal government still maintains that medical marijuana is 
not an effective or desirable treatment for any medical condition despite significant contrary evidence. 



Cannabis as illustrated in Kohler's book of 
medicinal plants from 1 897 




Medical cannabis 43 

Clinical applications 

A 2002 review of medical literature by Franjo Grotenhermen states 
that medical cannabis has established effects in the treatment of 
nausea, vomiting, premenstrual syndrome, unintentional weight loss, 
insomnia, and lack of appetite. Other "relatively well-confirmed" 
effects were in the treatment of "spasticity, painful conditions, 
especially neurogenic pain, movement disorders, asthma, [and] 
glaucoma". 

Preliminary findings indicate that cannabis-based drugs could prove 

Victoria , the United States first legal medical 

useful in treating adrenal disease, inflammatory bowel disease, marijuana plant grown by The Wo/Men's 

migraines, fibromyalgia, and related conditions. Alliance for Medical Marijuana. 

Medical cannabis has also been found to relieve certain symptoms of 

multiple sclerosis and spinal cord injuries by exhibiting antispasmodic and muscle-relaxant properties as 

well as stimulating appetite. 

Other studies state that cannabis or cannabinoids may be useful in treating alcohol abuse, amyotrophic lateral 
sclerosis, collagen-induced arthritis, asthma, atherosclerosis, bipolar disorder, colorectal 

cancer, HIV- Associated Sensory Neuropathy, depression, dystonia, epilepsy, digestive 

diseases, gliomas, hepatitis C, Huntington's disease, leukemia, skin tumors, 

methicillin-resistant Staphylococcus aureus (MRSA), Parkinson's disease, pruritus, posttraumatic stress 

disorder (PTSD), psoriasis, sickle-cell disease, sleep apnea, and anorexia nervosa. Controlled 
research on treating Tourette syndrome with a synthetic version of THC called (Marinol), showed the patients taking 
the pill had a beneficial response without serious adverse effects; other studies have shown that cannabis "has no 
effects on tics and increases the individuals inner tension". Case reports found that cannabis helped reduce tics, 
but validation of these results requires longer, controlled studies on larger samples. 

A study done by Craig Reinarman surveyed people in California who used cannabis found they did so for many 
reasons. Reported uses were for pain relief, muscle spasms, headaches, anxiety, nausea, vomiting, depression, 
cramps, panic attacks, diarrhea, and itching. Others used cannabis to improve sleep, relaxation, appetite, 
concentration or focus, and energy. Some patients used it to prevent medication side effects, anger, involuntary 
movements, and seizures, while others used it as a substitute for other prescription medications and alcohol. 

Recent studies 

Safety of cannabis 

From The Lancet, "There are no confirmed published cases worldwide of human deaths from cannabis poisoning, 
and the dose of THC required to produce 50% mortality in rodents is extremely high compared with other commonly 
used drugs". 

According to Associate Professor Emeritus of Psychiatry at Harvard Medical School Lester Grinspoon, "When 
cannabis regains its place in the US Pharmacopeia, a status it lost after the passage of the Marijuana Tax Act of 
1937, it will be seen as one of the safest drugs in that compendium". 

There are medical reports of occasional infarction, stroke and other cardiovascular side effects. Marijuana's 
cardiovascular effects are not associated with serious health problems for most young, healthy users. Researchers 
have reported in the International Journal of Cardiology, "Marijuana use by older people, particularly those with 
some degree of coronary artery or cerebrovascular disease, poses greater risks due to the resulting increase in 
catecholamines, cardiac workload, and carboxyhemoglobin levels, and concurrent episodes of profound postural 
hypotension. Indeed, marijuana may be a much more common cause of myocardial infarction than is generally 



Medical cannabis 44 

recognized. In day-to-day practice, a history of marijuana use is often not sought by many practitioners, and even 
when sought, the patient's response is not always truthful. Thus, clinicians should be more vigilant in inquiring about 
use of marijuana in their patients, particularly among the younger adults who may present with cardiac events in the 
absence of cardiovascular disease or other obvious risk factors.' 

A 2012 study published in JAMA and funded by National Institutes of Health looked at a population of over 5,115 
American men and women to see whether smoked cannabis has effects on the pulmonary system similar to those 
from smoking tobacco. The researchers found "Occasional and low cumulative marijuana use was not associated 
with adverse effects on pulmonary function." Smoking an average of one joint a day for seven years, they found, did 
not worsen pulmonary health. 

Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to 
that found in tobacco smoke or cigars. Over fifty known carcinogens have been identified in cannabis smoke. 
These include nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene. Marijuana 
smoke was listed as a cancer agent in California in 2009. 

A 2006 study involving 1,212 incident cancer cases and 1,040 cancer- free controls found no causative link to oral, 
laryngeal, pharyngeal, esophageal or lung cancer when adjusting for several confounding factors including cigarette 
smoking and alcohol use. 

Regarding the relative safety of cannabis, former US DEA chief administrative law judge Judge Francis Young said: 

"There is no record in the extensive medical literature describing a proven, documented cannabis-induced 
fatality.... Despite [a] long history of use and the extraordinarily high numbers of social smokers, there are 
simply no credible medical reports to suggest that consuming marijuana has caused a single death. In practical 
terms, marijuana cannot induce a lethal response as a result of drug-related toxicity.... Marijuana's therapeutic 
ratio is impossible to quantify because it is so high.... Marijuana, in its natural form, is one of the safest 
therapeutically active substances known to man." Wikipedia: Identifying reliable sources 

Pain relief 

The effectiveness of cannabis as an analgesic has been the subject of numerous studies. University of Oxford doctors 
found that the brain on THC showed reduced response to pain, suggesting that the the drug may help patients endure 
pain. Brain scans showed reduced activity in two centers of the brain where pain is registered: The mid- Anterior 

cingulate cortex and the right Amygdala. However, cannabis did not block the sensation of pain like morphine-based 

T521 T531 

pain killers. The researchers also found a great degree of variation among individual reports of pain relief. 

According to Stuart Silverman, M.D., a rheumatologist at Cedars-Sinai Medical Center, "Historically and 
anecdotally, marijuana has been used as a painkiller". A Canadian study showed cannabis can reduce "nerve 
pain" from surgical complications or injuries. The study's twenty-one subjects suffered from chronic pain and 
patients who smoked cannabis with a 9.4% THC content reported less pain than those patients who smoked the 
placebo. Improved quality of sleep and reduced anxiety were other reported benefits. Igor Grant, psychiatrist and 
director of the Center for Medicinal Cannabis Research at the University of California San Diego, has stated, "There 
is good evidence now that cannabinoids may be either an adjunct or a first-line treatment". Grant explained further 
that not everyone experienced pain relief, but the percentage of people who did was comparable to those who said 
that they experienced relief from other medications commonly prescribed for neuropathic pain (the subject of his 
study), such as antidepressants. 

A small-scale UCSF study found that patients with chronic pain may experience greater relief if cannabinoids were 

added to an opiate-only treatment regime. The findings further suggested that combination therapy could result in 

T571 
reduced opiate dosages. The College of Physicians and Surgeons at Columbia University, U.S. published a study 

in the Neuropsychopharmacology journal in 2013 that is based on research that was conducted with fifteen males 

and fifteen females who smoked marijuana every day. The study's subjects were exposed to either a placebo, inhaled 

marijuana, or dronabinol, a pill that contains cannabis' psychoactive ingredient. Participants were monitored to 



Medical cannabis 



45 



ensure that they had not smoked in the time period immediately prior to the tests and did not have other drugs 
(including alcohol) in their systems. The researchers concluded that "Dronabinol administration decreased pain 
sensitivity and increased pain tolerance that peaked later and lasted longer relative to smoked marijuana", thereby 
providing evidence that the pill form was superior to smoked cannabis in terms of pain relief efficacy. However, the 
Columbia researchers further stated, " A primary caveat of the current findings is that the study population consisted 
of daily marijuana smokers; this study limitation should be considered when interpreting the findings and placing 
them within the context of the potential therapeutic feasibility of cannabinoids [for the general population]. 



,,[58] 



Glaucoma 

In glaucoma, cannabis and THC have been shown to reduce 
intra-ocular pressure (IOP) by an average of 24% in people with 
normal IOP who have visual-field changes. In studies of healthy adults 
and glaucoma patients, IOP was reduced by an average of 25% after 
smoking a cannabis "cigarette" that contained approximately 2% 
THC — a reduction as good as that observed with most other 
medications available today, according to a review by the Institute of 
Medicine. 

In a separate study, the use of cannabis and glaucoma was tested and 

found that the duration of smoked or ingested cannabis or other 

cannabinoids is very short, averaging 3 to 3.5 hours. Their results showed that for cannabis to be a viable therapy, 

the patient would have to take in cannabis in some form every 3 hours. They said that for ideal glaucoma treatment it 




Medical cannabis in edible form 



would take two times a day at most for compliance purposes from patients. 



[60] 



Spasticity in multiple sclerosis 

A review of six randomized controlled trials of a combination of THC 

and CBD extracts for the treatment of multiple sclerosis (MS) related 

muscle spasticity reported, "Although there was variation in the 

outcome measures reported in these studies, a trend of reduced 

spasticity in treated patients was noted." The authors postulated that 

"cannabinoids may provide neuroprotective and anti-inflammatory 

benefits in MS." A small study done on whether or not cannabis could 

be used to control tremors of MS patients was conducted. The study 

found that there was no noticeable difference of the tremors in the 

patients. Although there was no difference in the tremors the patients 

felt as if their symptoms had lessened and their quality of life had improved. The researchers concluded that the 

mood enhancing or cognitive effects that cannabis has on the brain could have given the patients the effect that their 




tremors were getting better. 



□[61] 



Medical cannabis 



46 



Alzheimer's disease 

Research done by the Scripps Research Institute in California shows 
that the active ingredient in marijuana, THC, prevents the formation of 
deposits in the brain associated with Alzheimer's disease. THC was 
found to prevent an enzyme called acetylcholinesterase from 
accelerating the formation of "Alzheimer plaques" in the brain more 
effectively than commercially marketed drugs. THC is also more 
effective at blocking clumps of protein that can inhibit memory and 
cognition in Alzheimer's patients, as reported in Molecular 
Pharmaceutics. Cannabinoids can also potentially prevent or slow the 
progression of Alzheimer's disease by reducing tau protein 
phosphorylation, oxidative stress, and neuroinflammation. 




Cannabinoids found in medical cannabis prevent 
or inhibit the progression of Alzheimer's 
disease. 



A 2012 review from the Philosophical Transactions of a Royal Society 

B suggested that activating the cannabinoid system may trigger an "anti-oxidant cleanse" in the brain by removing 
damaged cells and improving the efficiency of the mitochrondria. The review found cannabinoids may slow decline 
in age and disease-related cognitive functioning. 

Breast cancer 




According to a 2007 and a 2010 study at the California Pacific Medical 

Center Research Institute, cannabidiol (CBD) stops breast cancer from 

spreading throughout the body by downregulating a gene called ID1. 

This may provide a non-toxic alternative to chemotherapy while 

achieving the same results without the painful and unpleasant side 

effects. The research team says that CBD works by blocking the 

activity of a gene called ID1, which is believed to be responsible for a 

process called metastasis, which is the aggressive spread of cancer 

cells away from the original tumor site. According to findings 

released by the team in 2012, when the particularly aggressive 

"triple-negative" cells (which contain high levels of ID1 and account 

for 15% of breast cancers) were exposed to CBD, they "not only stopped acting 'crazy' but also returned to a healthy 



^&®&$&^^% 



Medical cannabis blocks the spread of breast 
cancer by downregulating a gene called ID1. 



normal state". Human trial models are currently in development 
commented: 



[64] 



Dr Sean McAllister, study co-leader, 



"The preclinical trial data is very strong, and there's no toxicity. There's really a lot of research to move ahead 
with and to get people excited". 



Medical cannabis 



47 




HIV/AIDS 

Investigators at Columbia University published clinical trial data in 

2007 showing that HIV/AIDS patients who inhaled cannabis four times 

daily experienced substantial increases in food intake with little 

evidence of discomfort and no impairment of cognitive performance. 

They concluded that smoked cannabis has a clear medical benefit in 

HIV-positive patients. In another study in 2008, researchers at the 

University of California, San Diego School of Medicine found that 

marijuana significantly reduces HIV-related neuropathic pain when 

added to a patient's already-prescribed pain management regimen and 

may be an "effective option for pain relief" in those whose pain is not 

controlled with current medications. Mood disturbance, physical 

disability, and quality of life all improved significantly during study treatment. Despite management with opioids 

and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in 

HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to 

modulate pain perception. No serious adverse effects were reported, according to the study published by the 

American Academy of Neurology. A study examining the effectiveness of different drugs for HIV associated 

neuropathic pain found that smoked Cannabis was one of only three drugs that showed evidence of efficacy. 



Medical cannabis helps to alleviate pain and to 
improve quality of life for HIV-positive 
patients. 



Brain cancer 

A study by Complutense University of Madrid found the chemicals in 
cannabis promote the death of brain cancer cells by essentially helping 
them feed upon themselves in a process called autophagy. The research 
team discovered that cannabinoids such as THC had anticancer effects 
in mice with human brain cancer cells and in people with brain tumors. 
When mice with the human brain cancer cells received the THC, the 
tumor shrank. Using electron microscopes to analyze brain tissue taken 
both before and after a 26-to 30-day THC treatment regimen, the 
researchers found that THC eliminated cancer cells while leaving 
healthy cells intact. The patients did not have any toxic effects from the treatment; previous studies of THC for the 




THC found in medical cannabis eliminates brain 
cancer while leaving healthy brain cells intact. 





treatment of cancer have also found the therapy to be well tolerated. 



Opioid dependence 



Injections of THC eliminate dependence on opiates in stressed rats, 
according to a research team at the Laboratory for Physiopathology of 
Diseases of the Central Nervous System (France) in the journal 
Neuropsychopharmacology. Deprived of their mothers at birth, rats 
become hypersensitive to the rewarding effect of morphine and heroin 
(substances belonging to the opiate family), and rapidly become 
dependent. When these rats were administered THC, they no longer 
developed typical morphine-dependent behavior. In the striatum, a 
region of the brain involved in drug dependence, the production of 
endogenous enkephalins was restored under THC, whereas it 




Medical cannabis is useful in the prevention and 
treatment of opiate dependence. 



Medical cannabis 



48 



diminished in rats stressed from birth which had not received THC. Researchers believe the findings could lead to 
therapeutic alternatives to existing substitution treatments. 

In humans, drug treatment subjects who use cannabis intermittently are found to be more likely to adhere to 
treatment for opioid dependence. Historically, similar findings were reported by Edward Birch, who, in 1889, 
reported success in treating opiate and chloral addiction with cannabis. 



Controlling ALS symptoms 

The potential role of cannabis in treating symptoms of ALS (or Lou 
Gehrig's Disease) has been the subject of recent research. A survey 
was conducted on 131 people suffering from ALS. The survey asked if 
the subjects had used cannabis in the last 12 months to control some of 
their symptoms. Of the 131 subjects, 13 had used the drug in some 
form to control symptoms. The survey found that cannabis was 
moderately effective in reducing symptoms of appetite loss, 
depression, pain, spasticity, drooling and weakness, and the longest 
relief reported was for depression. The pattern of symptom relief was 
consistent with those reported by people with other conditions, 
including multiple sclerosis (Amtmann et al. 2004). 




Medical cannabis is moderately effective in 
reducing symptoms of Amyotrophic lateral 
sclerosis (ALS) (Lou Gehrig's Disease). 



Medicinal compounds 

Cannabis contains 483 compounds. At least 80 of these are cannabinoids, which are the basis for medical and 

scientific use of cannabis. This presents the research problem of isolating the effect of specific compounds and 
taking account of the interaction of these compounds. Cannabinoids can serve as appetite stimulants, antiemetics, 
antispasmodics, and have some analgesic effects. Six important cannabinoids found in the cannabis plant are 
tetrahydrocannabinol, tetrahydrocannabinolic acid, cannabidiol, cannabinol, (3-caryophyllene, and cannabigerol. 



Tetrahydrocannabinol 

Tetrahydrocannabinol (THC) is the primary compound responsible for 
the psychoactive effects of cannabis. The compound is a mild 

analgesic, and cellular research has shown the compound has 

T711 
antioxidant activity. THC is believed to interact with parts of the 

brain normally controlled by the endogenous cannabinoid 

neurotransmitter, anandamide. Anandamide is believed to play a role 

in pain sensation, memory, and sleep. 




H 3 C 



Chemical structure of tetrahydrocannabinol 
(THC) 



Medical cannabis 



49 



Cannabidiol 

Cannabidiol (CBD) is a major constituent of medical cannabis. CBD 
represents up to 40% of extracts of medical cannabis. Cannabidiol has 
been shown to relieve convulsion, inflammation, anxiety, cough, 
congestion and nausea, and it inhibits cancer cell growth. Recent 

studies have shown cannabidiol to be as effective as atypical 

T721 T731 

antipsychotics in treating schizophrenia and psychosis. Because 

cannabidiol relieves the aforementioned symptoms, cannabis strains 

with a high amount of CBD may benefit people with multiple sclerosis, 

frequent anxiety attacks and Tourette syndrome. 




Cannabidiol has been shown to relieve 

convulsions, inflammation, anxiety, cough, 

congestion and nausea, and it inhibits cancer cell 

growth. 



Cannabinol 

Cannabinol (CBN) is a therapeutic cannabinoid found in Cannabis 
sativa and Cannabis indica. It is also produced as a metabolite, or a 
breakdown product, of tetrahydrocannabinol (THC). CBN acts as a 
weak agonist of the CB and CB receptors, with lower affinity in 
comparison to THC. 




(J-Caryophyllene 

Part of the mechanism by which medical cannabis has been shown to reduce 
tissue inflammation is via the compound (3-caryophyllene. A cannabinoid 
receptor called CB2 plays a vital part in reducing inflammation in humans 
and other animals. (3-Caryophyllene has been shown to be a selective 
activator of the CB2 receptor. (3-Caryophyllene is especially concentrated in 
cannabis essential oil, which contains about 12—35% (3-caryophyllene. 

Cannabigerol 

Like cannabidiol, cannabigerol is not psychoactive. Cannabigerol has been 
shown to relieve intraocular pressure, which may be of benefit in the 
treatment of glaucoma. 




ch 3 

Chemical structure of (3-caryophyllene 



Medical cannabis 



50 




Cannabigerol. 



Pharmacologic THC and THC derivatives 

In the USA, the FDA has approved several cannabinoids for use as medical therapies: dronabinol (Marinol) and 
nabilone. These medicines are taken orally. 

These medications are usually used when first line treatments for nausea and vomiting associated with cancer 
chemotherapy fail to work. In extremely high doses and in rare cases "psychotomimetic" side effects are possible. 
The other commonly used antiemetic drugs are not associated with these side effects. 

Marinol's manufacturer stated on their website: "The most frequently reported side effects in patients with AIDS 
during clinical studies involved the central nervous system (CNS). These CNS effects (euphoria, dizziness, or 

T77ir7Rl 

thinking abnormalities, for example) were reported by 33% of patients taking MARINOL". Four documented 

fatalities resulting from Marinol have been reported. 

Canasol is a cannabis-based medication for glaucoma that relieves intraocular pressure symptoms associated with 
late- stage glaucoma. 

It was created by an ophthalmologist, Dr. Albert Lockhart and Dr. Manley E. West, and began distribution in 

roi 1TQ21 

1987. As of 2003, it was still being distributed in the United Kingdom, several US states, and several 

Caribbean nations. 

It is notable for being one of the first cannabis-containing pharmaceuticals to be developed for the modern 
pharmaceutical market and being one of the few such pharmaceuticals to have ever been legally marketed in the 
United States. [82][84] 

The prescription drug Sativex, an extract of cannabis administered as a sublingual spray, has been approved in 

Canada for the adjunctive treatment (use alongside other medicines) of both multiple sclerosis and cancer related 

pain. Sativex has also been approved in the United Kingdom, New Zealand, and the Czech Republic, and is 

r&^i r&7i r88i 
expected to gain approval in other European countries. William Notcutt is one of the chief researchers that 

has developed Sativex, and he has been working with GW and founder Geoffrey Guy since the company's inception 

in 1998. Notcutt states that the use of MS as the disease to study "had everything to do with politics." 



Medical cannabis 



51 



Medication 


Approval 


Country 


Licensed indications 


Cost 


Nabilone 


1985 


USA, Canada 


Nausea of cancer chemotherapy that has failed to respond 
adequately to other antiemetics 


US$4000.00 for a year's 
supply (in Canada) 


Canasol 


1987 


USA, Canada, several 
Caribbean nations 


Introcular pressure associated with late-stage Glaucoma 




Marinol 


1985 


USA 

Canada (1992) 


Nausea and vomiting associated with cancer chemotherapy in 
patients who have failed to respond adequately to conventional 
treatments 


US$652 for 30 doses @ 
10 mg online 


1992 


USA 


[91] 
Anorexia associated with AIDS-related weight loss 


Sativex 


1995 


Canada 


Adjunctive treatment for the symptomatic relief of neuropathic 
pain in multiple sclerosis in adults 


T921 
C$9,351 per year 1 J 


1997 


Canada 


Pain due to cancer 



Criticism 

One of the major criticisms of cannabis as medicine is opposition to smoking as a method of consumption. However, 
smoking is no longer necessary due to the development of healthier methods. Medicinal cannabis patients can use 
vaporizers, where the essential cannabis compounds are extracted and inhaled. In addition, edible cannabis, which is 
produced in various baked goods, is also available, and has demonstrated longer lasting effects. 

The United States Food and Drug Administration (FDA) issued an advisory against smoked medical cannabis 
stating that, "marijuana has a high potential for abuse, has no currently accepted medical use in treatment in the 
United States, and has a lack of accepted safety for use under medical supervision." The National Institute on Drug 
Abuse NIDA state that "Marijuana itself is an unlikely medication candidate for several reasons: (1) it is an 
unpurified plant containing numerous chemicals with unknown health effects; (2) it is typically consumed by 
smoking further contributing to potential adverse effects; and (3) its cognitive impairing effects may limit its 
utility". [94] 

The Institute of Medicine, run by the United States National Academy of Sciences, conducted a comprehensive 
study in 1999 to assess the potential health benefits of cannabis and its constituent cannabinoids. The study 
concluded that smoking cannabis is not recommended for the treatment of any disease condition, but did conclude 
that nausea, appetite loss, pain and anxiety can all be mitigated by marijuana. While the study expressed reservations 
about smoked cannabis due to the health risks associated with smoking, the study team concluded that until another 
mode of ingestion was perfected that could provide the same relief as smoked cannabis, there was no alternative. In 
addition, the study pointed out the inherent difficulty in marketing a non-patentable herb. Pharmaceutical companies 
will probably make less investments in product development if the result is not possible to patent. The Institute of 
Medicine stated that there is little future in smoked cannabis as a medically approved medication. The report also 

concluded that for certain patients, such as the terminally ill or those with debilitating symptoms, the long-term risks 

* f * [95] [96] 

are not or great concern. 

Marinol was less effective than the steroid megestrol in helping cancer patients regain lost appetites. A phase III 
study found no difference in effects of an oral cannabis extract or THC on appetite and quality of life (QOL) in 
patients with cancer-related anorexia-cachexia syndrome (CACS) to placebo. "Citing the dangers of cannabis and 
the lack of clinical research supporting its medicinal value" the American Society of Addiction Medicine in March 
2011 issued a white paper recommending a halt to using marijuana as a medicine in U.S. states where it has been 
declared legal. 



[][] 



Medical cannabis 52 

Mental disorders 

A study of 50,000 Swedish soldiers who had smoked at least once were twice as likely to develop schizophrenia as 
those who had not smoked. The study concluded that either smoking caused a higher rate of schizophrenia, or that 

mm 

those with schizophrenia were more likely to be drawn to cannabis. 

A study by Keele University commissioned by the British government found that between 1996 and 2005 there had 
been significant reductions in the incidence and prevalence of schizophrenia. From 2000 onwards there were also 
significant reductions in the prevalence of psychoses. The authors say this data is "not consistent with the hypothesis 
that increasing cannabis use in earlier decades is associated with increasing schizophrenia or psychoses from the 
mid-1990s onwards M . [100] 

A 10-year study on 1923 individuals from the general population in Germany, aged 14-24, concluded that cannabis 
use is a risk factor for the development of incident psychotic disorder symptoms, and the continued use might 
increase the risk. 

However a medical study published in 2009 taken by the Medical Research Council in London, showed there was no 
significant effect of THC on [HC]-raclopride binding. Thus concluding, recreational cannabis users do not release 
significant amounts of dopamine from an oral THC dose equivalent to a standard cannabis cigarette. This result 
challenges current models of striatal dopamine release as the mechanism mediating cannabis as risk factor for 
schizophrenia. 

Lung cancer and chronic obstructive pulmonary disease 

The evidence to date is conflicting as to whether smoking cannabis increases the risk of developing lung cancer or 
chronic obstructive pulmonary disease (COPD) among people who do not smoke tobacco. In 2006 a study by 
Hashibe, Morgenstern, Cui, Tashkin, et al. suggested that smoking cannabis does not, by itself, increase the risk of 
lung cancer. Many studies did report a strongly synergistic effect, however, between tobacco use and smoking 
cannabis such that tobacco smokers who also smoked cannabis dramatically increased their already very high risk of 
developing lung cancer or chronic obstructive pulmonary disease by as much as 300%. Some of these research 
results follow below: 

• In 2006, Hashibe, Morgenstern, Cui, Tashkin, et al presented the results from a study involving 2,240 subjects 
that showed non-tobacco users who smoked marijuana did not exhibit an increased incidence of lung cancer or 
head-and-neck malignancies. These results were supported even among very long-term, very heavy users of 
marijuana. Tashkin, a pulmonologist who has studied cannabis for 30 years, commenting in news reports in the 
lay media on the results of the study he co-authored, suggested, "It's possible that tetrahydrocannabinol (THC) in 
cannabis smoke may encourage apoptosis, or programmed cell death, causing cells to die off before they have a 
chance to undergo malignant transformation". He summarized the results found by his study, saying "We 
hypothesized that there would be a positive association between cannabis use and lung cancer, and that the 
association would be more positive with heavier use. What we found instead was no association at all, and even a 
suggestion of some protective effect." 

• A case-control study involving 79 cases and 324 controls looked at lung cancer in adults 55 years of age and 
younger, and found the risk of lung cancer increased 8% (95% confidence interval (CI) 2-15) for each joint-year 
of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 
5-9) for each pack-year of cigarette smoking, after adjustment for confounding variables including cannabis 
smoking. 

• A 2008 study by Hii, Tarn, Thompson, and Naughton found that cannabis smoking leads to asymmetrical bullous 
disease, often in the setting of normal CXR and lung function. In subjects who smoke cannabis, these pathological 
changes occur at a younger age (approximately 20 years earlier) than in tobacco smokers. However this study 
involved only 10 patients who also smoked tobacco and had symptoms of the disease prior to the study. There 



Medical cannabis 53 

was no control group in the study. The Journal of the Royal Society of Medicine in 2004 found insufficient 
evidence for a causative link between cannabis smoke and bullous disease. 

• Researchers from the University of British Columbia presented a study at the American Thoracic Society 2007 
International Conference showing that smoking cannabis and tobacco together more than tripled the risk of 
developing COPD over just smoking tobacco alone.Wikipedia:Identifying reliable sources 

(medicine) Wikipedia:Link rot Similar findings were released in April 2009 by the Vancouver Burden of 
Obstructive Lung Disease Research Group. The study reported that smoking both tobacco and cannabis 
synergistically increased the risk of respiratory symptoms and COPD. Smoking only cannabis, however, was not 
associated with an increased risk of respiratory symptoms of COPD. In a related commentary, pulmonary 
researcher Donald Tashkin wrote, "...we can be close to concluding that cannabis smoking by itself does not lead 
toCOPD M . [110] 

Method of consumption 

The harm caused by smoking can be minimized or eliminated by the 

use of a vaporizer^ or ingesting the drug in an edible form. Vaporizers 

are devices that heat the active constituents to a temperature below the 

ignition point of the cannabis, so that their vapors can be inhaled. 

Combustion of plant material is avoided, thus preventing the formation 

of carcinogens such as poly aromatic hydrocarbons, benzene and 

carbon monoxide. A pilot study led by Donald Abrams of UC San 

Francisco showed that vaporizers eliminate the release of irritants and 

toxic compounds, while delivering equivalent amounts of THC into the 

bloodstream. According to Matthew Seamon and his co-authors 

"Vaporizers are the optimal route of administration because they allow for rapid and complete absorption with 

minimal combustible byproducts, often considered the major health risk associated with smoking tobacco." 

In order to kill microorganisms, especially the molds A. fumigatus, A. flavus and A. niger, Levitz and Diamond 
suggested baking marijuana at 150 °C (302 °F) for five minutes. They also found that tetrahydrocannabinol (THC) 
was not degraded by this process. 

Pharmaceutical products 

• Nabiximols (US AN, trade name Sativex) is an aerosolized mist for oral administration intended for the 
treatment of pain. 

Reclassification 

A number of medical organizations have endorsed reclassification of marijuana to allow for further study. These 
include, but are not limited to: 

• The American Medical Association 

• The American College of Physicians - America's second largest physicians group 

• Leukemia & Lymphoma Society — America's second largest cancer charity 

• American Academy of Family Physicians opposes the use of marijuana except under medical supervision 

Other medical organizations recommend a halt to using marijuana as a medicine in U.S. 

• The American Society of Addiction Medicine 




Medical cannabis 



54 



History 

Ancient China and Taiwan 

Cannabis, called ma JS (meaning "hemp; cannabis; numbness") or 
ddmd ~)\ M (with "big; great") in Chinese, was used in Taiwan for 
fiber starting about 10,000 years ago. The botanist Li Hui-Lin 

wrote that in China, "The use of Cannabis in medicine was probably a 
very early development. Since ancient humans used hemp seed as 
food, it was quite natural for them to also discover the medicinal 
properties of the plant." The oldest Chinese pharmacopeia, the (ca. 
100 CE) Shennong Bencaojing # jR ^ Jf£ M ("Shennong's 
Materia Medica Classic"), describes dama "cannabis". 



The use of cannabis, at least as fiber, has been 

shown to go back at least 10,000 years in Taiwan. 

"Da ma" (Pinyin pronunciation) is the Chinese 

expression for cannabis, the first character 

meaning "big" and the second character meaning 

"hemp." 



The flowers when they burst (when the pollen is scattered) 

are called Jftlf [mafen] or Jfti^J [mabo]. The best time 

for gathering is the seventh day of the seventh month. The 

seeds are gathered in the ninth month. The seeds which have entered the soil are injurious to man. It 

grows in [Taishan] (in [Shandong] ...). The flowers, the fruit (seed) and the leaves are officinal. The 

leaves and the fruit are said to be poisonous, but not the flowers and the kernels of the seeds. 

Emperor Shen-Nung, who was also a pharmacologist, wrote a book on treatment methods in 2737 that included the 
medical benefits of cannabis. He recommended the substance for many ailments, including constipation, gout, 
rheumatism, and absent-mindedness. Hua Tuo lived many years later, yet he is credited with being the first person 
known to use cannabis as an anesthetic. He reduced the plant to powder and mixed it with wine for 
administration. In China, the era of Han Western, the 3rd century the great surgeon Hua Tuo conducts operations 
under anesthesia using Indian hemp. The Chinese term for anesthesia (JSE @¥: ma zui ) is also composed of the 
ideogram which means hemp, followed by means of intoxication. Elizabeth Wayland Barber says the Chinese 
evidence "proves a knowledge of the narcotic properties of Cannabis at least from the 1st millennium B.C." when 
ma was already used in a secondary meaning of "numbness; senseless." "Such a strong drug, however, suggests that 

the Chinese pharmacists had now obtained from far to the southwest not THC-bearing Cannabis sativa but Cannabis 

IT 221 
indica, so strong it knocks you out cold. 

Cannabis is one of the 50 "fundamental" herbs in traditional Chinese medicine, and is prescribed to treat diverse 
indications. 

Every part of the hemp plant is used in medicine; the dried flowers (fft), the achenia (jf ), the seeds (JiS 
t), the oil (Jft ?S), the leaves, the stalk, the root, and the juice. The flowers are recommended in the 
120 different forms of (J5L feng) disease, in menstrual disorders, and in wounds. The achenia, which are 
considered to be poisonous, stimulate the nervous system, and if used in excess, will produce 
hallucinations and staggering gait. They are prescribed in nervous disorders, especially those marked by 
local anaesthesia. The seeds, by which is meant the white kernels of the achenia, are used for a great 
variety of affections, and are considered to be tonic, demulcent, alterative, laxative, emmenagogue, 
diuretic, anthelmintic, and corrective. They are made into a congee by boiling with water, mixed with 
wine by a particular process, made into pills, and beaten into a paste. A very common mode of 
exhibition, however, is by simply eating the kernels. It is said that their continued use renders the flesh 
firm and prevents old age. They are prescribed internally in fluxes, post-partum difficulties, aconite 
poisoning, vermillion poisoning, constipation, and obstinate vomiting. Externally they are used for 
eruptions, ulcers, favus, wounds, and falling of the hair. The oil is used for falling hair, sulfur poisoning, 
and dryness of the throat. The leaves are considered to be poisonous, and the freshly expressed juice is 
used as an anthelmintic, in scorpion stings, to stop the hair from falling out and to prevent it from 



Medical cannabis 



55 



turning gray. They are especially thought to have antiperiodic properties (prevention of regular 
recurrence of the symptoms of a disease). The stalk, or its bark, is considered to be diuretic, and is used 
with other drugs in gravel. The juice of the root is used for similar purposes, and is also thought to have 
a beneficial action in retained placenta and post-partum hemorrhage. An infusion of hemp (for the 
preparation of which no directions are given) is used as a demulcent drink for quenching thirst and 
relieving fluxes. 



Ancient Egypt 

The Ebers Papyrus (ca. 1550 BCE) from Ancient Egypt describes 
medical cannabis. Other ancient Egyptian papyri that mention 
medical cannabis are the Ramesseum III Papyrus (1700 BC), the Berlin 
Papyrus (1300 BC) and the Chester Beatty Medical Papyrus VI (1300 
BC). The ancient Egyptians even used hemp (cannabis) in 

suppositories for relieving the pain of hemorrhoids. Around 2,000 
B.C., the ancient Egyptians used cannabis to treat sore eyes. The 
egyptologist Lise Manniche notes the reference to "plant medical 
cannabis" in several Egyptian texts, one of which dates back to the 
eighteenth century BCE. 



[127] 



Ramesseum III Papyrus (1700 BC) 

Papyrus Ramassei III, col. 26: 

K.t phr.t: m3t.t smsm.t qnqn, sdr n i3d.t, i c ir.ty n=s im dw3y 

Alia praecepta: parsley, hemp and obey, in the dew of rest, wash eyes 

in that early in the morning 



^iin~± r ?i^M^~Q^ - 



TCASvkji* , ■ 






The Ebers Papyrus (ca. 1550 BCE) from Ancient 

Egypt has a prescription for medical marijuana 

applied directly for inflammation 



Ancient India 

Cannabis was a major component in religious practices in ancient India as well as in medicinal practices. For many 
centuries, most parts of life in ancient India incorporated cannabis of some form. Surviving texts from ancient India 
confirm that cannabis' psychoactive properties were recognized, and doctors used it for treating a variety of illnesses 

and ailments. These included insomnia, headaches, a whole host of gastrointestinal disorders, and pain: cannabis was 

ri28i 
frequently used to relieve the pain of childbirth. One Indian philosopher expressed his views on the nature and 

uses of bhang (a form of cannabis), which combined religious thought with medical practices. "A guardian lives in 

the bhang leaf... To see in a dream the leaves, plant, or water of bhang is lucky... A longing for bhang foretells 

happiness. It cures dy sentry and sunstroke, clears hlegm, quickens digestion, sharpens appetite, makes the tongue of 

the lisper plain, freshens the intellect and gives alertness to the body and gaiety to the mind. Such are the useful and 

needful ends for which in His goodness the Almighty made bhang.." 



Medical cannabis 



56 



Ancient Greece 

The Ancient Greeks used cannabis to dress wounds and sores on their 
horses. In humans, dried leaves of cannabis were used to treat nose 
bleeds, and cannabis seeds were used to expel tapeworms. The most 
frequently described use of cannabis in humans was to steep green 
seeds of cannabis in either water or wine, later taking the seeds out and 
using the warm extract to treat inflammation and pain resulting from 
obstruction of the ear. 

In the 5th century BCE Herodotus, a Greek historian, described how 

the Scythians of the Middle East used cannabis in steam baths. These 

[] 




The Ancient Greeks used cannabis not only for 

human medicine, but also in veterinary medicine 

to dress wounds and sores on their horses. 



baths drove the people to a frenzied state. 
South East Asia 

Patani from Asia are primary natural producers of the diuretic, antiemetic, antiepileptic, anti-inflammatory, pain 
killing and antipyretic properties of Cannabis sativa, and used it extensively for 'Kopi Kapuganja' and 'Pecel Ganja', 



as recreation food, drinks and relaxing medication for centuries. 



[citation needed] 



Medieval Islamic world 

In the medieval Islamic world, Arabic physicians made use of the diuretic, antiemetic, antiepileptic, 
anti-inflammatory, Analgesic and antipyretic properties of Cannabis sativa, and used it extensively as medication 



from the 8th to 18th centuries. 



[129] 




Cannabis sativa from Vienna Dioscurides, 512 
AD 



Medical cannabis 



57 



Modern history 

An Irish physician, William Brooke O'Shaughnessy, is credited with 
introducing the therapeutic use of cannabis to Western medicine. He 
was Assistant-Surgeon and Professor of Chemistry at the Medical 
College of Calcutta, and conducted a cannabis experiment in the 
1830s, first testing his preparations on animals, then administering 
them to patients to help treat muscle spasms, stomach cramps or 
general pain 



[] 




Medical cannabis ad from Sweden (1800) 



Cannabis as a medicine became common throughout much of the 

Western world by the 19th century. It was used as the primary pain 

reliever until the invention of aspirin. Modern medical and scientific inquiry began with doctors like 

O'Shaughnessy and Moreau de Tours, who used it to treat melancholia and migraines, and as a sleeping aid, 

analgesic and anticonvulsant. At the local level authorities introduced various laws that required the mixtures that 

contained cannabis, that was not sold on prescription, must be marked with warning labels under the so-called poison 

laws. 

A Swedish lexicon printed in 1912 describes cannabis drug and cannabis extract as a now with us deserted method 
for medical treatment. 



There were at least 2000 cannabis medicines prior to 1937 with over 

n 32] 

280 manufacturers . 



CANNABIS AMERICANA 

a s. p. 



Physiologically Tested 



^ It the 




I T is ho longer necessary 
to depend on ihe for- 
eign raficCy which is <)( 
h ^h etisi jiTid slinhiljr su- 
perior. The iinoernlnry 
of further supplies at it i; 
a nuth-cr Factor iavon n£ 
I be American product. 



An advertisement for cannabis americana 
distributed by a pharmacist in New York in 1917. 



Later in the century, researchers investigating methods of detecting 

cannabis intoxication discovered that smoking the drug reduced 

intraocular pressure. In 1955 the antibacterial effects were 

described at the Palacky University of Olomouc. Since 1971 Lumir 

Ondfej Hanus was growing cannabis for his scientific research on two 

large fields in authority of the University. The marijuana extracts were 

then used at the University hospital as a cure for aphthae and haze. 

In 1973 physician Tod H. Mikuriya reignited the debate concerning 

cannabis as medicine when he published "Marijuana Medical Papers". High intraocular pressure causes blindness in 

glaucoma patients, so he hypothesized that using the drug could prevent blindness in patients. Many Vietnam War 

veterans also found that the drug prevented muscle spasms caused by spinal injuries suffered in battle. Later 

medical use focused primarily on its role in preventing the wasting syndromes and chronic loss of appetite associated 

with chemotherapy and AIDS, along with a variety of rare muscular and skeletal disorders. 

In 1964, Dr. Albert Lockhart and Manley West began studying the health effects of traditional cannabis use in 
Jamaican communities. They discovered that Rastafarians had unusually low glaucoma rates and local fishermen 
were washing their eyes with cannibis extract in the belief that it would improve their sight. Lockhart and West 
developed, and in 1987 gained permission to market, the pharmaceutical Canasol: one of the first to cannabis 
extracts. They continued to work with cannabis throughout the years, developing more pharmaceuticals and 

TR91 

eventually receiving the Jamaican Order of Merit for their work. 

Later, in the 1970s, a synthetic version of THC was produced and approved for use in the United States as the drug 
Marinol. It was delivered as a capsule, to be swallowed. Patients complained that the violent nausea associated with 
chemotherapy made swallowing capsules difficult. Further, along with ingested cannabis, capsules are harder to 
dose-titrate accurately than smoked cannabis because their onset of action is so much slower. Smoking has remained 
the route of choice for many patients because its onset of action provides almost immediate relief from symptoms 
and because that fast onset greatly simplifies titration. For these reasons, and because of the difficulties arising from 
the way cannabinoids are metabolized after being ingested, oral dosing is probably the least satisfactory route for 



Medical cannabis 58 

cannabis administration. Relatedly, some studies have indicated that at least some of the beneficial effects that 
cannabis can provide may derive from synergy among the multiplicity of cannabinoids and other chemicals present 
in the dried plant material. Such synergy is, by definition, impossible with respect to the use of 

single-cannabinoid drugs like Marinol. 

During the 1970s and 1980s, six U.S. states' health departments performed studies on the use of medical cannabis. 
These are widely considered some of the most useful and pioneering studies on the subject. Vcitatlon nee e Voters in 
eight states showed their support for cannabis prescriptions or recommendations given by physicians between 1996 
and 1999, including Alaska, Arizona, California, Colorado, Maine, Michigan, Nevada, Oregon, and Washington, 
going against policies of the federal government. In May 2001, "The Chronic Cannabis Use in the 

Compassionate Investigational New Drug Program: An Examination of Benefits and Adverse Effects of Legal 

Clinical Cannabis" (Russo, Mathre, Byrne et al.) was completed. This three-day examination of major body 

ri38i 
functions of four of the five living US federal cannabis patients found "mild pulmonary changes" in two patients. 

National and international regulations 

Medical use of cannabis or preparation containing THC as the active 

substance is legalized in Canada, Belgium, Austria, Netherlands, UK, 

Spain, Israel, Finland and some states in the U.S., although it is still * pi^ 

illegal under U.S. federal law. "7 



> 




4± 

Cannabis is in Schedule IV of the United Nations" Single Convention 

on Narcotic Drugs, making it subject to special restrictions. Article 2 Worldwide laws on cannabis possession for 

provides for the following, in reference to Schedule IV drugs: medical P ur P oses - 

A Party shall, if in its opinion the prevailing conditions in its 

country render it the most appropriate means of protecting the public health and welfare, prohibit the 
production, manufacture, export and import of, trade in, possession or use of any such drug except for 
amounts which may be necessary for medical and scientific research only, including clinical trials therewith to 
be conducted under or subject to the direct supervision and control of the Party. 

The convention thus allows countries to outlaw cannabis for all non-research purposes but lets nations choose to 
allow medical and scientific purposes if they believe total prohibition is not the most appropriate means of protecting 
health and welfare. The convention requires that states that permit the production or use of medical cannabis must 
operate a licensing system for all cultivators, manufacturers and distributors and ensure that the total cannabis market 
of the state shall not exceed that required "for medical and scientific purposes." 

Africa 

Cannabis has been used in Africa since at least the 15th century. Its use was introduced by Arab traders, somehow 
connected to India. "In Africa, the plant was used for snake bite, to facilitate childbirth, malaria, fever, blood 
poisoning, anthrax, asthma, and dysentery." (Zuardi, 2006, 4) Though African governments have tried to limit and 
stop its use, it still seems to be deeply ingrained, mostly through religious rituals. 

Austria 

9 9 

In Austria both A -THC and pharmaceutical preparations containing A -THC are listed in annex V of the Narcotics 

Decree (Suchtgiftverordnung). Compendial formulations are manufactured upon prescription according to the 

German Neues Rezeptur-Formularium. 

On 9 July 2008, the Austrian Parliament approved cannabis cultivation for scientific and medical uses. Cannabis 
cultivation is controlled by the Austrian Agency for Health and Food Safety (Osterreichische Agentur fur 
Gesundheit und Ernahrungssicherheit, AGES). 



Medical cannabis 



59 



Canada 

In Canada, the regulation on access to cannabis for medical purposes, established by Health 
Canada in February 2000, defines two categories of patients eligible for access to medical 
cannabis. BC College of Physicians and Surgeons' recommendation, as well as the CMPA 
position, is that physicians may prescribe cannabis if they feel comfortable with it. The 
MMAR forms are a confidential document between Health Canada, the physician and the 
patient. The information is not shared with the College or with the RCMP. No doctor has 
ever gone to court or faced prosecution for filling out a form or for prescribing medical 
cannabis. Category 1 covers any symptoms treated within the context of providing 
compassionate end-of-life care or the symptoms associated with different medical 
conditions. Category 2 is for applicants who have debilitating symptom(s) of medical 
condition(s), other than those described in Category 1. The application of eligible patients 
must be supported by a medical practitioner. 







III 


1 

Fu 


ii] 



Centre compassion de 
Montreal, au Quebec. 



[143] 



The cannabis distributed by Health Canada is provided under the brand CannaMed by the company Prairie Plant 
Systems Inc. In 2006, 420 kg of CannaMed cannabis was sold, representing an increase of 80% over the previous 
year. However, patients complain of the single strain selection as well as low potency, providing a pre-ground 
product put through a wood chipper (which deteriorates rapidly) as well as gamma irradation and foul taste and 
smell. 

It is also legal for patients approved by Health Canada to grow their 
own cannabis for personal consumption, and it's possible to obtain a 
production license as a person designated by a patient. Designated 
producers were permitted to grow a cannabis supply for only a single 
patient, however. That regulation and related restrictions on supply 
were found unconstitutional by the Federal Court of Canada in January 
2008. The court found that these regulations did not allow a sufficient 
legal supply of medical cannabis, and thus forced many patients to 
purchase their medicine from unauthorized, black market sources. This 
was the eighth time in the previous ten years that the courts ruled 
against Health Canada's regulations restricting the supply of the 
medicine. On 14 Dec 2012 the Canadian government announced 
plans to overhaul its rules regarding medical cannabis 

In Canada there are four forms of medical cannabis. The first one is a cannabis extract called Sativex that contains 
THC and cannabidiol in a spray form. The second is a synthetic or manmade THC called dronabinol marketed as 
Marinol. The third also a synthetic version of THC called nabilone that is called Cesamet on the markets. The fourth 
product is the herbal form of cannabis often referred to as marijuana. 




Reception desk at the Kingston Compassion Club 
Society in Kingston, Ontario 



Medical cannabis 



60 



Czech Republic 

Medical use of cannabis has been legal and regulated in the Czech republic since the 1 April 2013. 

Germany 

In February 2008, seven German patients could legally be treated with medicinal cannabis, distributed by 
prescription in pharmacies. To regulate therapeutic use, Germany modeled on Dutch neighbor who distributes 
this way since in 2003 (120 kg in 2008). 

In Germany dronabinol was rescheduled in 1994 from annex I to annex II of the Narcotics Law 
(Betaubungsmittelgesetz) in order to ease research; in 1998 dronabinol was rescheduled from annex II to annex III 
and since then has been available by prescription, whereas A -THC is still listed in annex I. Manufacturing 
instructions for dronabinol containing compendial formulations are described in the Neues Rezeptur-Formularium. 



Israel 

Marijuana for medical use has been permitted in Israel since the early 
1990s for cancer patients and those with pain-related illnesses such as 
Parkinson's, multiple sclerosis, Crohn's Disease, other chronic pain and 
post- traumatic stress disorder. Patients can smoke the drug, ingest it in 
liquid form, or apply it to the skin as a balm. The numbers of patients 
authorized to use marijuana in Israel in 2012 is about 10,000. 



[][] 



There are eight government- sanctioned cannabis growing operations in 
Israel, which distribute it for medical purposes to patients who have a 
prescription from a doctor, via either a company's store, or in a medical 
center. 

THC, the psychoactive chemical component in marijuana that causes a 
high, was first isolated by Israeli scientists Raphael Mechoulam of the 
Hebrew University in Jerusalem's Center for Research on Pain and 
Yechiel Gaoni of the Weizmann Institute in 1964 



[][] 



The Tikkun Olam company has developed a variety of marijuana that 
is reported to provide the medical benefits of cannabis, but without 
THC. The cannabis instead contains high quantities of CBD, a 
substance that is believed to be an anti-inflammatory ingredient, which 
helps alleviate pain. 




Professor Raphael Mechoulam and Yechiel 

Gaoni isolated THC from Cannabis in 1964 and 

later discovered anandamide. 



Netherlands 

Since 2003, the country's pharmacies 
distribute medicinal cannabis 

(pharmaceutical form of the natural 
plant) by prescription, in addition to 
other drugs containing cannabinoids 
(dronabinol, Sativex). 

The four therapeutic qualities produced 
by the company Bedrocan and 
distributed in the pharmacy are: 

• Bedrocan (18% dronabinol / THC. + <1% Cannabidiol / CBD) 




Prescription Bedica medical cannabis in the Netherlands 



Medical cannabis 



61 



• Bedica (14% dronabinol / THC. + <1% Cannabidiol / CBD) granules 

• Bediol (11% dronabinol / THC. + <1% Cannabidiol / CBD) 

• Bedrobinol (6% dronabinol / THC. + 7.5% Cannabidiol / CBD) granules 




Spain 

In Spain, since the late 1990s and early 2000s, medical cannabis underwent a process of progressive 
decriminalization and legalisation. The parliament of the region of Catalonia was the first in Spain to have voted 
unanimously in 2001 legalizing medical marijuana; it was quickly followed by parliaments of Aragon and the 
Balearic Islands. nee e The Spanish Penal Code prohibits the sale of cannabis but it does not prohibit 

consumption (although consumption on the street is fined). Until early 2000, the Penal Code did not distinguish 
between therapeutic use of cannabis and recreational use, however, several court decisions show that this distinction 
is increasingly taken into account by judges. From 2006, the sale of seed is legalized, ltatwn nee e the sale and 
public consumption remains illegal, and private cultivation and use are permitted to associations. 

Several studies have been conducted to study the effects of cannabis on patients suffering from diseases like cancer, 
AIDS, multiple sclerosis, seizures or asthma. This research was conducted by various Spanish agencies at the 
Universidad Complutense de Madrid headed by Manuel Guzman, the hospital of La Laguna in Tenerife led 
neurosurgeon Luis Gonzalez Feria or the University of Barcelona. ^ Cltatwn 

Several cannabis consumption clubs and user associations have been established throughout Spain. These clubs, the 
first of which was created in 1991, are non-profit associations who grow cannabis and sell it at cost to its members. 
The legal status of these clubs is uncertain: in 1997, four members of the first club, the Barcelona Ramon Santos 
Association of Cannabis Studies, were sentenced to 4 months in prison and a 3000 euro fine, while at about the same 
time, the court of Bilbao ruled that another club was not in violation of the law. The Andalusian regional government 
also commissioned a study by criminal law professors on the "Therapeutic use of cannabis and the creation of 
establishments of acquisition and consumption. The study concluded that such clubs are legal as long as they 
distribute only to a restricted list of legal adults, provide only the amount of drugs necessary for immediate 
consumption, and not earn a profit. The Andalusian government never formally accepted these guidelines and the 
legal situation of the clubs remains insecure. In 2006 and 2007, members of these clubs were acquitted in trial for 
possession and sale of cannabis and the police were ordered to return seized crops. 



United Kingdom 

In England and Wales, the use of cannabis medicinally is accepted as a mitigating factor under Sentencing Council 
guidelines, if it is being cultivated or found in possession of someone. However, in the United Kingdom, 

possession of small quantities of cannabis does not usually warrant an arrest or court appearance (street cautions or 
fines are often given out instead). Under UK law, certain cannabinoids are permitted medically, but these are 
strictly controlled with many provisos under the Misuse of Drugs Act 1971 (in the 1985 amendments). 

The British Medical Association's official stance is "users of cannabis for medical purposes should be aware of the 
risks, should enrol for clinical trials, and should talk to their doctors about new alternative treatments; but we do not 
advise them to stop.' 



Medical cannabis 



62 




III II I II II II II II III I II II I II I II 



2) United States Patent 



United States 

In the United States federal level of government, cannabis per se has 
been made criminal by implementation of the Controlled Substances 
Act which classifies cannabis as a Schedule I drug, the strictest 
classification on par with heroin, LSD and ecstasy, and the Supreme 
Court ruled in 2005 that the Commerce Clause of the U.S. Constitution 
allowed the government to ban the use of cannabis, including medical 
use. The United States Food and Drug Administration states 
"marijuana has a high potential for abuse, has no currently accepted 
medical use in treatment in the United States, and has a lack of 
accepted safety for use under medical supervision". 

Two American (for-profit) companies, Cannabis Science Inc., and 
Medical Marijuana, Inc., are working towards getting FDA approval 
for cannabis based medicines (including smoked cannabis). Cannabis 
Science Inc. wants to have medical cannabis approved by the FDA so 
anyone, regardless of state, will have access to the medicine. Also, 
there is one non-profit organization, the Multidisciplinary Association 
for Psychedelic Studies (MAPS) working towards getting Cannabis 
approved by the FDA for PTSD. 

Since the medical marijuana movement began, twenty states and the 

District of Columbia, starting with California in 1996, have legalized 

medical cannabis or effectively decriminalized it: Alaska, Arizona, 

California, Colorado, Connecticut, Delaware, Hawaii, 

Maine, Massachusetts, Michigan, Montana, Nevada, New 

Jersey, New Mexico, Oregon, Rhode Island, Vermont, 

Virginia, Washington; and Washington D.C. Maryland allows 

for reduced or no penalties if cannabis use has a medical 

basis. Despite its legality in Washington, and Colorado, an 

employee can still be fired if they test positive on a drug test, despite 

having a doctor's recommendation. California, Colorado, New 

Mexico, Maine, Rhode Island, Montana, and Michigan are currently 

the only states to utilize dispensaries to sell medical cannabis. Connecticut will be the eighth but has yet to issue any 

licenses. California's medical cannabis industry took in about $2 billion a year and generated $100 million in state 

sales taxes during 2008 with an estimated 2,100 dispensaries, co-operatives, wellness clinics and taxi delivery 

services in the sector colloquially known as "cannabusiness". 



Related U.S. Application Du 






-fee 



The Health and Human Services Division of the 
Federal government of the United States holds a 
patent US 6630507 for medical cannabis. 



Some individual states such as Oregon choose to issue medical marijuana cards to residents with a doctors 
recommendation after paying a fee. 

On 19 October 2009 the US Deputy Attorney General issued a US Department of Justice memorandum to "All 
United States Attorneys" providing clarification and guidance to federal prosecutors in US States that have enacted 
laws authorizing the medical use of marijuana. The document is intended solely as "a guide to the exercise of 
investigative and prosecutorial discretion and as guidance on resource allocation and federal priorities." The US 
Deputy Attorney General David W. Ogden provided seven criteria, the application of which acts as a guideline to 
prosecutors and federal agents to ascertain whether a patient's use, or their caregiver's provision, of medical cannabis 

"represents part of a recommended treatment regiment consistent with applicable state law", and recommends 
against prosecuting patients using medical cannabis products according to state laws. Not applying those criteria, the 



Medical cannabis 63 

Dep. Attorney General Ogden concludes, would likely be "an inefficient use of limited federal resources". The 
memorandum does not change any laws. Sale of cannabis remains illegal under federal law. The U.S. Food and 
Drug Administration's position, that marijuana has no accepted value in the treatment of any disease in the United 

c . . i i i .t [citation needed] 

States, has also remained the same. 

The Health and Human Services Division of the federal government holds a patent US 6630507 for medical 

cannabis. The patent, "Cannabinoids as antioxidants and neuroprotectants", issued October 2003 reads: 

Cannabinoids have been found to have antioxidant properties, unrelated to NMD A receptor antagonism. This new found property makes 
cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, 
inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting 
neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as 
Alzheimer's disease, Parkinson's disease and HIV dementia... . 

On 17 November 2011, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR part 404.7(a)(l)(i), the National 
Institutes of Health, Department of Health and Human Services, published in the Federal Register, that it is 
contemplating the grant of an exclusive patent license to practice the invention embodied in U.S. Patent 6,630,507, 
entitled "Cannabinoids as antioxidants and neuroprotectants" and PCT Application Serial No. PCT/US 99/08769 and 
foreign equivalents thereof, entitled "Cannabinoids as antioxidants and neuroprotectants" [HHS Ref. No. 
E-287-1997/2] to KannaLife Sciences Inc., which has offices in New York, U.S. This patent and its foreign 
counterparts have been assigned to the Government of the United States of America. The prospective exclusive 
license territory may be worldwide, and the field of use may be limited to: The development and sale of 

cannabinoid(s) and cannabidiol(s) based therapeutics as antioxidants and neuroprotectants for use and delivery in 

[1721 
humans, for the treatment of hepatic encephalopathy, as claimed in the Licensed Patent Rights. 

References 

[5] cannabismd.net (http://www.cannabismd.net/antibiotic-properties/). cannabismd.net. Retrieved on 2013-04-17. 

[6] Medical Marijuana I Strains (http://www.canadamedicalmarijuana.com/medical-marijuana-strains.html). Canadamedicalmarijuana.com. 

Retrieved on 2013-04-17. 
[39] Grotenhermen, Russo (2002) "Review of Therapeutic Effects." Chapter 1 1, p. 128 in Cannabis and Cannabinoids: Pharmacology, 

Toxicology, and Therapeutic Potential, Routledge, ISBN 0789015080. 
[46] JAMA Network I JAMA I Association Between Marijuana Exposure and Pulmonary Function Over 20 Years (http://jama.jamanetwork. 

com/article. aspx?articleid= 1104848) 
[51] Francis L. Young (http://www.druglibrary.org/schaffer/library/studies/YOUNG/index.html). Druglibrary.org (1988-09-06). Retrieved 

on 2013-04-17. 
[61] AMA meeting: Delegates support review of marijuana's schedule I status; A change could make it easier for researchers to test potential 

medical uses and develop a drug delivery form safer than smoking, (http://www.ama-assn.org/amednews/2009/ll/23/prsell23.htm) By 

Kevin B. O'Reilly, American Medical News. 30 November 2009 
[62] Szalavitz, Maia. (2012-10-29) How Cannabinoids May Slow Brain Aging I TIME.com (http://healthland.time.com/2012/10/29/ 

how-cannabinoids-may-slow-brain-aging/#ixzz2IGnHWiQ0). Healthland.time.com. Retrieved on 2013-04-17. 
[63] The endocannabinoid system in normal and pathological brain ageing (http://rstb.royalsocietypublishing.org/content/367/1607/3326. 

abstract). Rstb.royalsocietypublishing.org (2012-12-05). Retrieved on 2013-04-17. 
[78] Marinol (http://www.fda.gov/ohrms/dockets/dockets/05n0479/05N-0479-emc0004-04.pdf). fda.gov (September 2004). 
[80] Stepper, H. P., Department of Health and Human Services (24 August 2005) Letter to Mr. Yablan (http://medicalmarijuana.procon.org/ 

sourcefiles/marinol.pdf). medicalmarijuana.procon.org 
[82] Dr Farid F. Youssef. "Cannibis Unmasked: What it is and why it does what it does". UWIToday: June 2010. http://sta.uwi.edu/uwitoday/ 

archive/june_20 1 0/article9 . asp 
[83] Evans, T. "Ganja-based eyedrops a hot sell." (http://jamaica-gleaner.com/gleaner/20030824/lead/lead3.html) The Gleaner (Jamaica). 24 

August 2003. 
[84] Eulalee Thompson. "Seeing through ganja" (http://jamaica-gleaner.com/gleaner/20010129/news/news2.html). The Gleaner (Jamaica). 

29 January 2001 
[86] Cooper, Rachel." GW Pharmaceuticals launches world's first prescription cannabis drug in Britain (http://www.telegraph.co.uk/finance/ 

newsbysector/pharmaceuticalsandchemicals/7842794/GW-Pharmaceuticals-launches-worlds-first-prescription-cannabis-drug-in-Britain. 

html)" The Telegraph. 21 June 2010. Retrieved 15 May 2011. 



Medical cannabis 64 

[87] " Sativex Approved in New Zealand (http://www.gwpharm.com/Sativex Approved in New Zealand for the Treatment of Spasticity due to 

Multiple Sclerosis. aspx)" GW Pharmaceuticals. 3 Nov.2010. Retrieved 15 May 2011. 
[88] " Sativex Approved in the Czech Republic (http://www.gwpharm.com/Sativex Approved in the Czech Republic. aspx)" GW 

Pharmaceuticals. 15 April 2011. Retrieved 15 May 2011. 
[102] Can recreational doses of THC produce significant dopamine release in the human striatum? http://www.ncbi.nlm.nih.gov/pubmed/ 

19539765?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Epub 2009 Jun 17. 
[107] Bullous disease of the lung and cannabis smoking: insufficient evidence for a causative link (http://www.ncbi.nlm.nih.gov/pmc/ 

articles/PMC 1360494/) 
[114] United States Adopted Names Coincil: Statement on a nonproprietary name (http://www.ama-assn.org/amal/pub/upload/mm/365/ 

nabiximols.pdf) 
[119] Li, Hui-Lin (1974). "An Archaeological and Historical Account of Cannabis in China", Economic Botany 28.4:437-448, p. 444. 
[120] Bretschneider, Emil (1895). Botanicon Sinicum: Notes on Chinese Botany from Native and Western Sources. Part III, Botanical 

Investigations in the Materia Medica of the Ancient Chinese. Kelly & Walsh, p. 378 (http://books.google.com/ 

books ?id=256gAAAAMAAJ&pg=PA378&lpg=PA378#v=onepage&q=&f=false). 
[122] Barber, Elizabeth Wayland. (1992). Prehistoric Textiles: The Development of Cloth in the Neolithic and Bronze Ages with Special 

Reference to the Aegean. Princeton University Press, p. 38. 
[123] Smith, Frederick Porter (1911). Chinese Materia Medica: Vegetable Kingdom. Shanghai: American Presbyterian Mission Press, pp. 90-91. 
[126] (Webley, Kayla. "Brief History: Medical Marijuana." Time 21 June 2010.) 

[127] Lise Manniche, An Ancient Egyptian Herbal, University of Texas Press, 1989, ISBN 978-0-292-70415-2 

[132] The Antique Cannabis Book (http://antiquecannabisbook.com/). antiquecannabisbook.com (16 March 2012). Retrieved 2012-05-19. 
[146] http://www.ipolitics.ca/2012/12/14/health-canada-getting-out-of-the-marijuana-trade/ 
[148] Zdravotnictvi prochazi zmenou. Lecba konopim je nyni legalni I Zpravy z domova (http://www.lidovky.cz/ 

ve-zdravotnictvi-nabyva-ucinnosti-rada-zmen-lecba-konopim-legalni-104-/zpravy-domov.aspx?c=A130401_124139_ln_domov_hm). 

www.lidovky.cz. Retrieved on 2013-04-17. 
[149] Radio Prague - News - 01-04-2013 21:30 (http://www.radio.ez/en/section/news/news-2013-04-01#3). Radio.cz. Retrieved on 

2013-04-17. 
[150] Germany: First Patients to Receive cannabis from the pharmacy, IACM-Bulletin of 15 February 2009 (http://www.cannabis-med.org/ 

english/nav/home-bulletin.htm). www.cannabis-med.org (1 October 2003). Retrieved 2012-05-19. 
[153] News: ISRAEL VALLEY SANTE - Les vertus du cannabis - En Israel, le « fournisseur medical » de marijuana du Ministere de la sante, 

Tikun Olam, prone les bienfaits de la plante controversee pour le traitement du cancer (http://web.archive.Org/web/20110102025045/http:/ 

/www.israelvalley.com/news/2010/11/22/29283/ 

israelvalley-sante-les-vertus-du-cannabis-en-israel-le-fournisseur-medical-de-marijuana-du-ministere-de-la-sante-tikun-ol). Israelvalley.com- 

Site officiel de la Cambre de Commerce France-Israel, CCFI (22 November 2010). Retrieved 2012-05-19. 
[154] Hidalgo, Susana (01-03-2009). "El debate sobre el cannabis no espabila." (http://www.publico.es/espana/205176/ 

el-debate-sobre-el-cannabis-no-espabila) Publico.es 
[155] Perez-Lanzac C. (12 September 2008) El cannabis pelea por un espacio legal, (http://www.elpais.com/articulo/sociedad/cannabis/ 

pelea/espacio/legal/elpepisoc/20081209elpepisoc_l/Tes) El Pais. 
[157] http://worldwide.espacenet.com/textdoc?DB=EPODOC&IDX=US6630507 
[165] NORML- 
[168] The Times - California dreaming of full marijuana legalisation (http://business.timesonline.co.uk/tol/business/industry_sectors/ 

health/article6851523.ece), The Times, 28 September 2009 

Further reading 

• Iversen, Leslie L. (2000). The Science of Marijuana. Oxford University Press. ISBN 0-19-513123-1. 

• 2009 Conference on Cannabinoids in Medicine, International Association for Cannabis as Medicine (http:// 
www.cannabis-med.org/meeting/Cologne2009/reader.pdf) 

• Cabral, Guy A. (2001). "Marijuana and Cannabinoids: Effects on Infections, Immunity, and AIDS". Journal of 
Cannabis Therapeutics 1 (3-4): 61-85. doi: 10.1300/J175v01n03_06 (http://dx.doi.org/10.1300/ 
J175v01n03_06). See also its alternate publication: Cabral, Guy A. (2001). "Marijuana and cannabinoids: effects 
on infections, immunity, and AIDS" (http://books. google. com/books ?hl=en&lr=&id=qUMQqalPT4QC& 
oi=fnd&pg=PA61). In Ethan Russo. Cannabis therapeutics in HIV/AIDS. Routledge. pp. 61—85. 

ISBN 978-0-7890-1699-7. 

• Watson SJ, Benson JA, Joy JE (2000). "Marijuana and medicine: assessing the science base: a summary of the 
1999 Institute of Medicine report". Archives of General Psychiatry 51 (6): 547—52. doi: 
10.1001/archpsyc.57.6.547 (http://dx.doi.Org/10.1001/archpsyc.57.6.547). PMID 10839332 (http://www. 



Medical cannabis 65 

ncbi.nlm.nih.gov/pubmed/10839332). 

• "References on Multiple Sclerosis and Marijuana" (http://www.druglibrary.org/schaffer/hemp/medical/ 
ms_mj_ref.htm). Schaffer Library of Drug Policy. 

• Tashkin, Donald P. (2001). "Effects of Smoked Marijuana on the Lung and Its Immune Defenses: Implications 
for Medicinal Use in HIV-infected Patients" (http://books. google. com/books ?id=qUMQqalPT4QC& 
lpg=PA87). In Ethan Russo. Cannabis therapeutics in HIV/AIDS. New York City: Haworth Press, pp. 87-102. 
ISBN 978-0-7890-1699-7. 

• Wujastyk, Dominik (12 September 2001). "Cannabis in Traditional Indian Herbal Medicine" (http://www.ucl. 
ac.uk/~ucgadkw/papers/cannabis.pdf). Retrieved 23 September 2009. 

• Joy, Janet E.; Watson, Stanley J.; Benson, John A., eds. (1999). Marijuana and Medicine: Assessing the Science 
Base (http ://www. nap. edu/openbook.php?isbn=030907 1550). Washington, D.C.: National Academies Press. 
ISBN 978-0-309-07155-0. OCLC 246585475 (http://www.worldcat.org/oclc/246585475). 

• Zuardi AW (2006). "History of cannabis as a medicine: a review" (http://www.scielo.br/pdf/rbp/v28n2/ 
29785.pdf). Revista Brasileira de Psiquiatria 28 (2): 153-7. doi: 10. 1590/S 15 16-44462006000200015 (http:// 
dx.doi.org/10.1590/S1516-44462006000200015). PMID 16810401 (http://www.ncbi.nlm.nih.gov/ 
pubmed/16810401). 

• Martinez, Martin (4 August 2008). "History of Medical Cannabis" (http://www.cannabismd.net/ 
history-of-medical-cannabis/). Retrieved 23 September 2009. 

• Aggarwal, Sunil K.; Carter, Gregory T.; Sullivan, Mark D.; ZumBrunnen, Craig; Morrill, Richard; Mayer, 
Jonathan D. (2009). "Medicinal use of cannabis in the United States: historical perspectives, current trends, and 
future directions" (https://docs.google.com/ 

fileview?id=OBzcIt01YbTHCZDBkZTA2NmItYmIlNSOOZjRkLTgxZDktYjFlYzY4YzJkMTk2&hl=en& 
pli=l). Journal of Opioid Management 5 (3): 153-68. PMID 19662925 (http://www.ncbi.nlm.nih.gov/ 
pubmed/ 19662925). Lay summary (http://blogs.sfweekly.com/thesnitch/2009/09/ 
chronic_city_summing_up_the_ev.php) - SF Weekly (15 September 2009). 

External links 

Marijuana: Gateway to Health (http://www.c-spanvideo.org/program/Gateway) Book discussion on C-SPAN 

by Clint Werner 

Medical cannabis (http://www.dmoz.org/Society/Issues/Health/Drugs/Illegal/Pro-Legalization/Marijuana/ 

Medical_Purposes//) at the Open Directory Project, links to websites about medical cannabis. 

Medical Marijuana: The Supremacy Clause, Federalism, and the Interplay Between State and Federal Laws 

(https://opencrs.com/document/R42398/) Congressional Research Service. 

The Center for Medicinal Cannabis Research of the University of California (http://www.cmcr.ucsd.edu/ 

geninf o/news . htm) . 

Bibliography on the use of medical cannabis in recent history (http://ahp.yorku.ca/?p=59) Advances in the 

History of Psychology, York University. 

The Forbidden Medicine (http://www.rxmarijuana.com/), an independent site operated by Harvard Medical 

School faculty members James Bakalar and Lester Grinspoon. 

Cannabis Health Journal (http://www.cannabishealth.com/) Online Medicinal Marijuana magazine based in 

British Columbia. 

Medical cannabis; Dutch Governments trail existing for 15 years. One patient (https://sites.google.com/site/ 

cannabismedicinalis/home) used 4 species for 1.5 years. 

(http://medicalmarijuana.procon.org/view. resource. php?resourceID=000881) Medical Marijuana in the U.S. 



Article Sources and Contributors 66 

Article Sources and Contributors 

Cannabinoid Source: http://en.wikipedia.org/w/index.php?oldid=557241911 Contributors: 32cllou, Aachaos, Abductive, Ajaxl51, Akofalvi, Alansohn, Algarcia85, Andrew Nutter, Anon lynx, 
AnthonyQBachler, Antrophica, Arcadian, Astavats, Avocado, Axl, BD2412, Barticus88, Beeshoney, Bendroz, BenrrlOl, Bensaccount, Big Bird, Biker Biker, Bobrayner, Bradgon, Bryan 
Derksen, CCIC, Cacycle, Cannabis, Centrx, Chemgirll31, Chris the speller, Christopherlin, Clarechenoweth, CliffC, Dagrun, David Hedlund, David.Throop, Dcirovic, Deli nk, Delighted eyes, 
Dmarquard, Doddy Wuid, Dougher, Drmies, Droll, Drpainless, Drphilharmonic, Duncanl69, E. Ripley, Edgarl81, Edward, Eekerz, Eequor, Enixl50, Eric Kvaalen, Extransit, Fborgnia, Ferre, 
Flaminhaz, Freakofnurture, Fred Bradstadt, Frozen Wind, Gaberdine2, Gaius Cornelius, Gene Nygaard, GeorgeLTirebiter, Gharmon, Glaman7, Gotz, Hadal, HappyCamper, Headbomb, 
HenryScow, Hiplibrarianship, Horoporo, Howrealisreal, Ilyse Kazar, Ioscius, Iownutopia, Itub, J.delanoy, J306, JWSchmidt, Jameskirby, Javal3690, Jeepday, Jeh, Jfdwolff, Jncraton, Jpvinall, 
Jrockley, Jrtayloriv, Jytdog, Kaf, Karn, Kingofoviedo, Kupirijo, Kwamikagami, Kwertii, Lazypplunite, LeaveSleaves, Lewisly, Leyo, Lothar von Richthofen, Luke poa, Lumir, MajorVariola, 
Mandarax, Maria mdv, Mearlon, Mendaliv, Meodipt, Mesoderm, Mikael Haggstrom, Minimac, Mpjl7, Mrholybrain, MudPhud, Mungox, Mushin, Natalya, Niceguyedc, Nnh, Nonantum, 
Nonsomniac, Nosforit, Nuujinn, Ohiostandard, OlEnglish, OldakQuill, Ombudsman, Ost316, Panoramix303, Papier K, Petrarchan47, Ph. eyes, Phil Ian Manning, PhilKnight, Pinethicket, Probios, 
Provider uk, Qnonsense, Radagast83, Renice, Rhetth, Rich Farmbrough, Rjanag, Rjwilmsi, Roadnottaken, RobArmstrong, S. Neuman, SalviaFan, Sapphic, Saric, Scarian, Scoticus, 
Seannyboy219, Shadowjams, ShelfSkewed, Shisha-Tom, Slowart, Smaines, Smartse, SqueakBox, St3vo, Starkl987, Subtropical-man, Subvertc, Tanevala, Tea with toast, Teles, Tgeller, 
TheBaur, Themfromspace, Tide rolls, Timotheus Canens, Tommy 2010, Tonytross, Train wreckwebb, Unyoyega, Verified72, Viridis Veritas, Vivio Testarossa, Vojtech.dostal, WadeSimMiser, 
Werson, Wicked licks, WickedSpice, WikiDao, Wormantson, X1987x, Zachjones4, Zane Russell,, 299 anonymous edits 

Distillation Source: http://en.wikipedia.org/w/index.php?oldid=558049218 Contributors: lOmetreh, 16@r, 2D, ABF, Abhisheks.nv, Acm, Agrawal.abhsihek, Alansohn, Alex297cat, Alexandria, 
Alfred Barnard, AlphaEta, Anaxial, Anbul21, Andre Engels, Animum, Antonrojo, Araku, Atomician, Audioiv, Azhura, BUF4Life, Baffle gabl978, Barek, Baristarim, BarrelProof, BeastRHIT, 
Beetstra, Ben Ben, BenC7, Betterusername, Big Brother 1984, Bill Owens Photography, Billinghurst, Blechnic, Bob, Bobol92, Bongwarrior, Brain40, Brian Crawford, Brygator, Bubba hotep, 
Buddy431, Bwrs, CERminator, CJHackett, COGDEN, Calabel992, Caltas, Canadian-Bacon, Candyland251, Canthusus, Capricorn42, Carl Henderson, Catmerl, Cblack2, Charles Matthews, 
Chem-awb, ChemE50, Chemical Engineer, Childzy, ChillDeity, Chinaranger, Chris fluppy, Cindy Jones 1, Closedmouth, Colonies Chris, Cometstyles, Conversion script, Copper-alembic, 
CopperKettle, Courcelles, D.c.camero, D3von, DGaw, DMacks, Daniele Pugliesi, Darrien, David Hedlund, David Justin, Dboy stein, Dbroadwell, Dbtfz, DerHexer, Dforest, Dillard421, 
Distortionmaster20, Dither 56, Dj Capricorn, DocWatson42, Doughtar, Drbreznjev, Dsmurat, Dvd-junkie, Dwmyers, East of Borschov, Edgarl81, ElationAviation, Elo69007, Epbrl23, 
EugeneForrester, Everytime, Excirial, Exor674, Falcon Kirtaran, Fanghong, FisherQueen, Fourthgeek, Fraggle81, Freakofnurture, Fril 17336, Funandtrvl, Funky Monkey, Fuzheado, Fse, 
Fealuinix, General Eisenhower, Gentgeen, Giftlite, Gilliam, Glacialfox, Glen, Glrx, GoShow, GoneAwayNowAndRetired, GregRM, Gtrmp, Gun Powder Ma, Gunslingerl812, Gurchzilla, 
Guruleninn, Gotz, H Bruthzoo, H Padleckas, HJ32, Hallenrm, Hallzer73, HappyApple, Harlandl, Hbackman, Hede2000, Hi878, Hmains, Homonation, Hooperbloob, Horst 75, Hugo Dufort, Ii 
SUPERNOVA, Ike9898, Ioscius, Itub, IvanLanin, Ixfd64, J Di, J. Patrick Fischer, J.delanoy, J8079s, JForget, JNW, Ja 62, Jacek Kendysz, JacobSpires98, Jagged 85, JamesB Watson, Jaxl, 
Jcarroll, Jebba, Jeraphine Gryphon, Jermonian, Jetul, Jfredrickson, Jfreyre, Jfurrl981, Jguk 2, Joe Rodgers, JoeSmack, Jose77, Joshsteiner, JoshuaZ, Jreferee, Jsimozar, Julesd, Juliancolton, Just 
Another Dan, KVDP, Karlhahn, Kbh3rd, Kdnl982, Kevin Dorner, KingAbdul, Kkolmetz, Knightl993, Knipptang, Konci, Koyaanis Qatsi, Kpjas, Ksyrie, KudzuVine, Kwertii, La goutte de pluie, 
Lasse Clausen, LeaveSleaves, Legajoe, Leonard G., Lightning, Lihaas, Little Mountain 5, Llywrch, LockeownzjOO, Lockesdonkey, Logan, Loonymonkey, LouisBB, Luna Santin, Lupin, 
LyleHoward, Lysy, MacGyverMagic, Mahanchian, Malikajumbe, Manager00104, Mandarax, Markpe, MassimoAr, Masteremoguy, Mat-C, Materialscientist, Mato, Mattchess, Mausy5043, 
Maximus Rex, Maziotis, Mbeychok, Megane, Melchoir, Mentifisto, Merenta, Merlinme, Michael Hardy, Mike Rosoft, Mike hayes, MiltonT, Minimac, Mur61j, Mzajac, Nahaj, Narutol990, 
Neelix, Neffk, Neutrality, Neverquick, NewEngland Yankee, News0969, Nicketje666, Nihiltres, Nijanand, Nitin70, Nonexistant User, Nunquam Dormio, Nuttycoconut, Oasisbob, Oatmeal 
batman, Oceanconsulting, Ohnoitsjamie, Ojayl23, Olivier, Omicronpersei8, Omsco, PaddyM, PamD, Paul P, Pdcook, Pekinensis, Peko, Pendimethalin, Peyre, Phantomsteve, Philip Trueman, 
Phoniexmofo, Physchim62, Piano non troppo, Pinethicket, Pinkadelica, Pinky si, PoccilScript, Poetaris, Polenth, Polyparadigm, Ponder, Prashanthns, Prodego, Pundesser, Quadell, 
Quantockgoblin, Qurozon, Qxz, RA0808, Randy549, Redoubts, Rerooks, Rich Farmbrough, Richard Harvey, Richard Taytor, Ridow, Rifleman 82, Rinroad, Rjwilmsi, Rocco8, Rossami, Rurik 
the Varangian, Ruy Pugliesi, SMC, Saga City, Sakagewea, Samchafin, Sansri, Sardanaphalus, Sasukel990, ScAvenger, ScaldingHotSoup, Schaber, Schfifty Three, Scientific29, Scottl4, 
Scottbogner, Sepideh7, Shalom Yechiel, SheeEttin, Shoessss, Sikkema, Skarebo, Skier Dude, Slashme, Sm0key82, Snigbrook, Snowolf, Squids and Chips, Stbalbach, Strontium5, 
Stuartamccormick, Swadeep.shrivastava, Syncategoremata, Syrthiss, TPK, Teecorbs, The Thing That Should Not Be, The wub, Thebigboyl, Tommy 2010, Torqmaster, TortoiseWrath, Trusilver, 
Tsemii, Unconcerned, User Al, V8rik, Van helsing, Veinor, Versus22, Vuo, WDavisl911, Weyes, Widr, Wiki Jared 21, Wikipelli, Willkingl979, Woland37, Wsloand, Wtmitchell, Zangala, 
Zigmar, Zundark, 783 anonymous edits 

Essential oil Source: http://en.wikipedia.org/w/index.php?oldid=552043863 Contributors: lbluerhino, 2over0, 3diwl9p02, 9tmaxr, ABF, Acroterion, Adrian J. Hunter, Ahoerstemeier, 
Alastairgbrown, Alexandrov, Alisonsage, ApersOn, Aroma-guide, AxelBoldt, BD2412, Barticus88, Bejnar, Belovedfreak, Beyoung, Biolandes, Bobol92, Bradensam, Brainsik, Brylletc, 
BullRangifer, Cacycle, CarolGray, Cayte, Cblack2, Ceyockey, Chachilongbow, Che090572, Chipl23456, Chobiche, Cindy Jonesl, Cmdrjameson, Colonies Chris, Corvus, Crouchs, Cybercobra, 
Cynthia Blue, Daniel5127, Darladeer, David.Throop, DavidSTaylor, Davidruben, Dbroadwell, DebKM, Declan.kenny, Dekimasu, Deli nk, Delldot, Dforest, Dhopeshwarsales, Dia A , Discott, 
Dmmaus, Duk, Dungodung, EODoc, ESkog, Edgarl81, Elvim, Eoilco, Erianna, Eric-Wester, Eskrima, Essentialdepot, Excirial, FF2010, FJPB, Feezo, Felix Stember, Fionnasmom, Foolestroupe, 
Foolishben, Francis Lima, FreplySpang, Futhark, G-13114, Gdaypal, Gene Nygaard, Giftlite, Gigemag76, Givrix, Gogo Dodo, Goodoodh, GraemeL, Gregalton, Groyolo, Habibibibalani, Hallows 
AG, Hangm n, Hannah-w, Hannah9, Hard2Win, Hardyplants, Hbackman, Headbomb, Herbjunkie, Honey badger 08, Huw Powell, Hyptis, Ice9ismine, Imc, Indon, Iridescent, JForget, 
JamesGrimshaw, Jamesfuhrman, Japeo, JeanGeilland, Jklamo, John Moss, Johnwikiupdater, Kabulykos, Kaidenj, Keenan Pepper, Kevinba99, Kfleisc, Khaled7stars, Khcbaser, Kintetsubuffalo, 
Kirper, Kmccoy, KojieroSaske, Kraftykyle, Kymacpherson, L Kensington, LarryMorseDCOhio, Lianiwidjaja, Liastnir, LoR. Caarl Robinson, Lobito09, Loniceas, LostAccount, Lottiotta, Luk, 
MGTom, Malcolma, Marsve, Mattchess, Maxx. scent, Mbeychok, Mccojr02, Mdurante, Melchoir, Methecooldude, Mgcsinc, Mike hayes, Mininannyl23, Mintleaf, Minwu, Mister Matt, Mkweise, 
Modify, Monirnstu, Mrtrey99, Mtruch, Mwanner, Mysid, Naniwako, Nehrams2020, Nick, Ninly, NorthamericalOOO, Ohnoitsjamie, Olav 10, Ootachi, Optimist on the run, Organic s4horses, 
Ost316, PKLpink, Palaeologos, Pamela J. Leavey, Phgao, Physchim62, PierreAbbat, Pinethicket, Plankwalking, PoliticalJunkie, Prestonmcconkie, Pyritie, Quarl, R'n'B, RDBrown, Requestion, 
Rewster, Ricardo Carneiro Pires, Rich Farmbrough, Rifleman 82, Rightleftright, Riley Clarke, Rjwilmsi, Robbiemuffin, Rolfs, Ronz, Room429, Ryanaxp, SandcatOl, Sannse, Sbula, Schlagwerk, 
Secret, Shandris, Shivaexportsindia, Shoefly, Six. oh. six, Sjschen, Slidinandridin06, Smalltowngirl, Smyth, Sochlo, Sodabrew, Steel, StradivariusTV, Stuartyeates, Surftheweb, TFOWR, 
Tabouretamtam, Tainter, Tarquin, TastyPoutine, Tedernst, Tejawe, Tempshill, Texture, Tfbybyhf, The Anome, The Parting Glass, The Thing That Should Not Be, Theofenton, Thorwald, Tide 
rolls, Tito4000, Total-MAdMaN, Totophe64, Tsalman, Typing monkey, TypoBoy, Unyoyega, Utcursch, Valoriejl, Veinor, Versageek, Viriditas, Vsmith, Vssun, Waitak, Walkerma, Wasell, 
Wavelength, Wendell, Wetman, Wfaulk, Whol23, Wjreece, Wmahan, Wolfkeeper, Wombatcat, Woohookitty, Wperdue, WriterHound, Zaian, Zorgkang, 357 anonymous edits 

Hash oil Source: http://en.wikipedia.org/w/index.php?oldid=557287649 Contributors: 2601:7:5780:6E:9550:6979:9CED:AB4A, AK50324, Acdx, AlanMl, Alchemist314, Alereon, Alpha 
Quadrant (alt), Andrew Lightbody, Anthony Appleyard, Anypodetos, Arjayay, Badsocref, Balou, Bgwhite, Bryan Derksen, Budurb, C-ray, C6541, Calabel992, Cantaloupe2, Chillum, Chondrite, 
Clawson, Crazynas, Cybercobra, DemonicPartyHat, DirkvdM, Firsfron, FonFon007, Foobar, FrO, France3470, Fredrik, FreplySpang, Gilliam, Glacialfox, Grendelkhan, Gotz, H, Hadal, 
Halogenated, Heah, Hillbillyholiday81, Hut 8.5, JHunterJ, JPmendo215, JWB, Jmlkl7, Jtkiefer, Kaden.anton, Kingbeer, Lamro, Litch, Lofor, Longhair, Macellarius, MichaelJanich, 
Middayexpress, Mjpresson, Mogism, Monty845, Mithrandir, Nick Number, Nono64, NorthamericalOOO, Patrick stud, Pedant, Petrarchan47, Phils, Philthypicker, Porcofederal, Portocinni, 
Psychonaut, R'son-W, RJFJR, Rastamees, Receptacle, Riffraffselbow, Rpyle731, ScottyBerg, Shaddack, SherpaSam, Shii, Shoessss, Skidoo, SqueakBox, TUF-KAT, Talibeynon, The Illusive 
Man, Thebestofall007, Tom harrison, Tommy 2010, Tristanb, Trliner, Ute in DC, Vjiced, Zujua, 181 anonymous edits 

Liquid-liquid extraction Source: http://en.wikipedia.org/w/index.php?oldid=556470350 Contributors: Acjelen, Anirluph, Anthony Appleyard, BD2412, Barkeep, Barticus88, Bob, 
Bobsodium, Boghog, Cacycle, Cadmium, Centrx, Chadnd, Chemeditor, Christian75, Cmdrjameson, DMacks, Dark Silver Crow, Dicklyon, Dirkb, Discospinster, Dougher, Drphilharmonic, Echis, 
Edgarl81, Elementl6, Epbrl23, Freestyle-69, Gaius Cornelius, GeeJo, Gene Nygaard, Gilderien, Hanter, Hemmingsen, Into The Fray, Itub, Jaerik, Janko, Jeancey, Jeff Dahl, John, Kafziel, 
Karlhahn, King of Hearts, Kkmurray, L Kensington, Mattchess, Mdhowe, Mets501, Michael Hardy, MikeParker, Mkadird, Morriswa, Nihiltres, Nono64, Notabletravel, Outsidelookin, 
Patricksears, Pengo, Petergans, Physchim62, Pinethicket, Polyamorph, Quantockgoblin, RJFJR, Rifleman 82, Rjwilmsi, RogerLie, Ronhjones, Seaphoto, Sensonet, Shaddack, Smokefoot, 
StephenBuxton, TenOfAUTrades, Tetracube, TheAMmollusc, Toddstl, Tonyl, Valoushka, Vchorozopoulos, Vornefeld, Vsmith, WOwOOr, Walkerma, Wavelength, WereSpielChequers, Z 
ShardZ, jLfol; JB, 125 anonymous edits 

Medical cannabis Source: http://en.wikipedia.Org/w/index.php ?oldid=5575 16735 Contributors: 01001, 14schltr, 2D, 4twenty42o, A8UDI, AED, Aamcoregon, Aaron Brenneman, Aaron 
kersten, Aaronbrick, Aaronisaflamer, AbsolutDan, Accounting4Taste, Achowat, Acjelen, Acroterion, Adamantios, Adambiswangerl, Adambro, AdultSwim, Adunl2, Agent Agent, Ahunt, 
Aillema, Ajnag, Ajor, Alakey2010, Alan Liefting, Alansohn, Alderman20, Alfie66, Alixcatl23, Allen3, Allen750, Aliens, AllstonTMitchell, Altogether, Ameliorate!, American2, Amh library, 
Amorrison08, Anarchist42, Anaxial, Andonic, Andrea. warzyniec, Angr, Anon lynx, Anonymoussell, Another Believer, AragonCandu, Argon233, Argos'Dad, ArielGold, Arjayay, Arm, Arthur 
Livermore, Artofscience, Asarelah, Asluby, Aspro, Astuishin, Asutt81215, Atroche, Aventinus, Avnjay, Awesomeo34, AxelBoldt, Axlq, BD2412, BMF81, Badanedwa, Badstoat, Baklarab, 
Balph Eubank, Bambicarle, Barek, Barentsz, Basrblog, Beetstra, Beland, Belovedfreak, Benjiboi, Benna, Bentogoa, Benwing, Bhadani, Bigo2013, Biker Biker, BlackTerror, Blanchardb, Blaxeep, 
Blazinl23, BlueZenith, Bmorris8745, Bobblewik, Bobol92, Bonadea, Boulevardier, Bplotkin, Bradylord, BranIL27, Brianski, BrokenSegue, Bryan Derksen, Bucketsofg, Budtrader, Bueller 007, 
BurnDownBabylon, CL8, CSWarren, CWenger, Cahk, Calieber, Calstar45, CambridgeBayWeather, Canis Lupus, CannabisNetwork, Cannabistina, Capricorn42, Captain-nOOdle, Carl Wagneer, 
Carlolsen, Caseyrdl, Cgaspare, Cgingold, Charcolgirl, Chase me ladies, I'm the Cavalry, Chaser, Chasingsol, Chondrite, Chq, Chris Capoccia, Chris the speller, ChrisGualtieri, ChrisHodgesUK, 
Chrisgedwards, Chrisjordancm, Christopherbrian, Chuck Sirloin, Cimmerian praetor, Cjsklionsl3, Ckatz, Clawson, Clintmct, Clubcanna, Cmdrjameson, Coaster420, Coinpeice, Collect, 
Conductivedan, Cooljuno411, Cory4782, Courcelles, Cpu420, Crabjuicer, Crazydeadbread, Creidieki, Crusher7, Cryptic, Czj, DGG, DJ Clayworth, DVdm, Da Best Editz, Dadaist6174, Dade 
ciku, Daedalic, Daemon8666, Daherb, Dakart, Daksya, Dalai la, Dale Arnett, Dammax07, Damyonl3, Dan Ros, Dan argo, Dan653, Dangerl23, Danheac, Daniel 1992, Daniel J. Leivick, 



Article Sources and Contributors 67 

Dannycas, Dante8, Dare7878, DarkEvil, Darth Panda, Darwinerasmus, Dave Runger, DaveScoundrel, Davecrosby uk, David Hedlund, David. Mestel, Davidkevin, Dawn Bard, Ddorian4004, 
DeadEyeArrow, Debresser, Defenseman Emeritus, Delirium, Delysidl26, DerHexer, DethmeOw, Devonmerryman, Dgw, Dianal991, DickClarkMises, DigitalMetaOl, DigitalNinja, Dilvie, Dino, 
Discospinster, DivaNtrainin, Docda, Doggiedayz, Doktorpdx, Dominated4Life, DonmikelO, Douglas Michael Massing, Dr.michael.benjamin, DrDeke, Drmies, Dro420, Drwarrior, Dudester508, 
Dustininsf, Dvmedis, Dycedarg, Dyingtogethigh, Dylan Inquisitor, Dysepsion, E Pluribus Americanus, Ebanaian, Eclectic hippie, Edgarl81, Edward, Edward321, Eeekster, Ego White Tray, 
Elmang, Eloquence, EoGuy, Epbrl23, Epicurus B., Eric Kvaalen, Ern malleyscrub, Escabared, Esowiki88, Estrella67, Et bravo, Evenios, Everard Proudfoot, Evil saltine, Exercisephys, Ezeu, 
Ezhiki, Falastine fee Qalby, Falcon8765, Fatass789, FayssalF, Fazzme, Ferre, Fieldday-sunday, Finlay McWalter, Fjstewartl, Flewis, Flora68, Flowanda, Frankenpuppy, Frankiix, Fredricktoo, 
Freecannabis, Freelance Intellectual, FreplySpang, Friendstotheworld, Friginator, Fuhghettaboutit, FunPika, Fvasconcellos, Gabbe, Gaius Cornelius, Galaxiaad, Galilsnap, Gamkiller, 
Gartenspinnen, Gatherton, Gdaviau32, Gditeam, Gekritzl, GeorgeLouis, GgrV, Gilliam, Ginsengbomb, Giraffedata, Gobonobo, Godotl3, Gogo Dodo, Goobergunch, Goofshow, Grantmidnight, 
Green Tanner, GreyTwilight, Griffeldo, Ground Zero, Grszll, Gtziavelis, Guanaco, Gumbygreen89, Gurch, Guy M, Gwernol, Gotz, HJ Mitchell, Haiduc, Hammersoft, Haridan, Harro5, Hbent, 
Heidimaus, Herbal Hi, Highlandsguy, Hiplibrarianship, Hiram408, Hmwith, Hodja Nasreddin, Hotcrocodile, House4556, Hoygan!!, Hughcharlesparker, Humphreyking, Hydriotaphia, Hypotron, 
II MusLiM HyBRiD II, IRP, Iamtheman69, IceflameO, Idril, Inter, Intrnal, Iowa.gybo, Iowawindow, Iridescent, J Di, J.A.McCoy, J.delanoy, J04n, JB supreme, JJJJust, JPMcGrath, JS747, 
JTBurman, JWSchmidt, JaGa, Jab843, Jackpots777, Jadewhit, Jafeluv, Jagged 85, Jahiegel, James084, Jarble, Jauerback, Jballan623, Jballentine, Jcheckler, Jedriffe, Jeff3000, JeffTheGeek, 
Jehfes, Jennavecia, Jeremiestrother, Jgreenberg, Jgwest, JhanCRUSH, Jim Klahr, Jiy, Jiyusan, Jkodadek, Jll, Jmilsl994, JoJan, Joao.caprivi, JoeSmack, Joffeloff, Joflynn, John, John Broughton, 
John Price, John Reaves, John254, Johnt7731, Josh333, Joshsimmons, Jossi, Jpeeling, Jrsharksll, Jrtayloriv, Jsorr, Julesd, Ka Faraq Gatri, Kaabi, Kaitlint, Kalqaatri, Kartano, Kathovo, Kazuba, 
Kdorlich, Keahapana, Keilana, Kelly, Kerem.atalay91, Kev58595, KevinScott, Kitsunegami, Knowledge Seeker, Kpstewart, Kris33, Kst447, Ktotam, Kubigula, Kukini, Kvng, Kyle Van Rees, 
Kylu, L Kensington, L31ackEyedAngels, LAX, LEGO BREAKER, LHcheM, La Pianista, Ladlergo, Ladyswayl985, LafinJack, Laurel Bush, Leif Stenberg, Lemworld, Lentower, 
LetTheSunshineln, Levineps, Liberlogos, Librsh, Lightmouse, Lilleybusiness, Limxzero, Linotte, Litebritel919, Little9a9, LizardJr8, Locos epraix, Loodog, Look2Seel, LordRM, Lostchicken, 
Lradrama, LuK3, Luckas Blade, Lugia2453, Lukobe, Lumir, Luna Santin, Lunaintern, MER-C, MMCWS, Madfingers88, Magichands, Mandersonl98, Marek69, Martarius, Martha p, Martin451, 
Maryjanemedicine, Mashford, Master Jay, Materialscientist, Mathew5000, Mattbr, Maxinater, Maxpowers4040, Maxxicum, Mbecker, Mboverload, Meaghan, Medische-wiet, MelbourneStar, 
Mentifisto, Meodipt, Merlin Matthews, Metalhead94, Mfield, Mgizewski, Mic 24, Michaellatulippe, MichiganTalisman, Midnight toboggan, Mikaey, Mike.gambol, MikeForbes, 
Mindovermatter77, Miss Madeline, MisterFine, Mistercow, Misty MH, Mjpresson, Mjquinn id, Mkweise, Mmsright21, Moin.max, Moleman2000, Moorlock, Mr Adequate, Mr. Wheely Guy, 
MrRadioGuy, Mrlego9, Msnicki, Mspuffnstuff420, Msruzicka, Muboshgu, Muhandes, Mulder416, Mungox, Muppet Apocalypse, Musicbooking, Musicman4534, Mygerardromance, Mzajac, 
N1RK4UDSK714, NSR, NTox, Nathansands, NawlinWiki, Nbauman, Neegermancontfook, Negativecreepl87, Neilc, Neuroscientist28, Neutrality, Newross, Nightkey, Nneonneo, 
Nnstonervibes, NoPetrol, Noformation, NorthamericalOOO, Notwist, Nsaa, Nulibrary, O'Dea, Oaksterdam, Ohconfucius, Ohiostandard, Ohnoitsjamie, Okaythere, OlEnglish, OldRight, Oliver202, 
Opiax, Optimale, Orangedolphin, Ostmoe, Ottawahitech, OverGrown420, OverlordQ, Ownlyanangel, PDH, Pairadox, Pakaran, Palmspringsbum, Pascal666, Pastafish, Patrick, Periclesof Athens, 
Petergkeyes, Petersam, Petrarchan47, PetterBudt, Pgalido, Phantomsnake, Philip Trueman, Piano non troppo, Pikiwyn, Pinethicket, Plasticup, Plautus satire, Pointedheels, Polarscribe, Poldavo, 
Pollinator, Pooleyl234, PopularMax, Portillo, Postdlf, Pregnantembryo, Proconorg, ProdigySportsman, Proofreader77, Prowler08, Pseudomonas, Psychonaught, Psyden, PuercoPop, 
Quackslikeaduck, Quialmademedoit, Quintote, QuiteUnusual, Qwfp, R'n'B, Rad Racer, Radzewicz, Rafti Institute, Razorflame, Rd232, Red, Redback22, Redondomax, Renice, Res2216firestar, 
ReverendG, Reverendmary, RexNL, Rhobite, Rich Farmbrough, Richwales, Rickjpelleg, Rivertorch, Rizalninoynapoleon, Rjanag, Rjwilmsi, Rlsheehan, Rmky87, Rmosler2100, RobertG, 
RobglOO, Rock nj, Rocketfairy, Roleplayer, Ron Duvall, Ropcat, Roswellmack, Roving Wordslinger, RoyBoy, Rreagan007, Rsheil, Rubricat, RubyQ, Runderwo, Rustiropez, SFK2, SJP, Sade, 
Sampi, Samuell, Sandstein, SandyGeorgia, Saudade7, Savantl3, Savecharlie, Sbblakey777, Scarbrtj, SchreiberBike, Scootey, ScottSteiner, Sebastian23, Seminshooter, Seventy Three, 
SexyVanillaFreshness, Sgeo, Shaddack, Shaun, Shelbowelbow, Shoeofdeath, Shoephonel, SilkTork, Silverxxx, Sionus, Sir towlie, Sjeng, Skamecrazyl23, Skarebo, Skier Dude, Skol221, Slakr, 
Sloggerbum, Smaines, Smalljim, Smurfdawg, Snigbrook, Snowolf, Snoyes, Soccerplayur012, Social tamarisk, Soldadito de Plomo, Soulparadox, Spacechickengrrl, SpliffsllOmb, SqueakBox, 
Squiquifox, Stephenb, Stevenmoseley, Stewart52ab, StrangerlnParadise, Subvertc, Sundaypinball, Sunny 256, Supertask, Svick, Svilen tomov, TDogg310, TUF-KAT, Tabletop, Tanzeel, 
Tbrinnand, Tea with toast, Thc420, The Interior, The Pot Snob, The Thing That Should Not Be, TheBaur, TheSmuel, Thebugmanl8, Theshibboleth, Thesuperpower, Thingg, Thsgrn, Tide rolls, 
TigerShark, Timeshifter, TitaniumDreads, Tnxman307, Tocino, Todfox, Tohd8BohaithuGhl, Tokerdesigner, Tonebowles, Tony Fox, Tonyl, Tonya420, Torchwoodwho, Torvik, Towel401, 
Tpipos, Treeofrock, TreezySamedi, Trevor Maclnnis, Trevorloflin, Triddle, Trinitresque, Trotter, Trusilver, Truthmissile, Tsomaria, Tstrobaugh, TurabianNights, Turkeyphant, Twsx, 
TylerDurden8823, Ubigcow, Ubsam, Ufukers, Ulricl313, Userwhosit, VBGFscJUn3, VQuakr, Vanished user svoinsr8wiraekfiu3rhnsfvr4sb, Vechs, Veggies, Videmus Omnia, VigilancePrime, 
Virapattra, Viridis Veritas, Viriditas, Vishnu2011, Voodoom, Vrd web services, Vrenator, Vsb, WAS 4.250, WJBscribe, WLU, Wadems, Walkaboutjones, Wardrubrecht, Wavelength, 
Wcallaway4, WeedConnection, Weel, West.andrew.g, Whig, Wiki alf, Wikipelli, Will.a.may, Williamfernandez, Wineland at central college, Wlmg, Wooyi, WriterHound, Wuhwuzdat, 
Wujastyk, Xavier86, Xcannabis, Xcyberxwolfx, Xgllo, Xnuala, Yamamoto Ichiro, Yelyos, Yonatan, YoungTesla, YourEyesOnly, Yoyokiller, Zanter, Zaslav, Zath42, Zero Diggity, Zklink, 
Zombie president, Zsinj, 1922 anonymous edits 



Image Sources, Licenses and Contributors 68 

Image Sources, Licenses and Contributors 

Image:CBG-type cannabinoid.png Source: http://en.wikipedia.org/w/index.php?title=File:CBG-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 Unported 

Contributors: Cacycle 

Image:CBG-type cyclization of cannabinoids.png Source: http://en.wikipedia.org/vv/index.php ?title=File:CBG-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 
Image:CBC-type cannabinoid.png Source: http://en.wikipedia.org/w/index.php?title=File:CBC-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 Unported 

Contributors: Cacycle 

Image:CBC-type cyclization of cannabinoids.png Source: http://en.wikipedia.org/w/index.php?title=File:CBC-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 
Image:CBD-type cannabinoid.png Source: http://en.wikipedia.org/vv/index.php ?title=File:CBD-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 Unported 

Contributors: Cacycle 

Image:CBD-type cyclization of cannabinoids.png Source: http://en.wikipedia.org/w/index.php?title=File:CBD-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 
Image:CBN-type cannabinoid.png Source: http://en.wikipedia.org/w/index.php?title=File:CBN-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 Unported 

Contributors: Cacycle 

Image:CBN-type cyclization of cannabinoids.png Source: http://en.wikipedia.org/w/index.php?title=File:CBN-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 
Image:CBE-type cannabinoid.png Source: http://en.vvikipedia.org/vv/index.php ?title=File:CBE-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 Unported 

Contributors: Cacycle 

Image:CBE-type cyclization of cannabinoids.png Source: http://en.vvikipedia.org/vv/index.php ?title=File:CBE-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 

Image:iso-CBN-type cannabinoid.png Source: http://en.wikipedia.org/w/index.php?title=File:Iso-CBN-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 
Unported Contributors: Cacycle 

Image:iso-CBN-type cyclization of cannabinoids.png Source: http://en.wikipedia.org/w/index.php?title=File:Iso-CBN-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 
Image:CBL-type cannabinoid.png Source: http://en.vvikipedia.org/vv/index.php ?title=File:CBL-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 Unported 

Contributors: Cacycle 

Image:CBL-type cyclization of cannabinoids.png Source: http://en.wikipedia.org/w/index.php?title=File:CBL-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 
Image:CBT-type cannabinoid.png Source: http://en.vvikipedia.org/vv/index.php ?title=File:CBT-type_cannabinoid.png License: Creative Commons Attribution-ShareAlike 3.0 Unported 

Contributors: Cacycle 

Image:CBT-type cyclization of cannabinoids.png Source: http://en.vvikipedia.org/vv/index.php ?title=File:CBT-type_cyclization_of_cannabinoids.png License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 

ImagerKolkata-Kut.jpg Source: http://en.vvikipedia.org/vv/index.php ?title=File: Kolkata-Kut.jpg License: Public Domain Contributors: Psychonaught (talk). Original uploader was 
Psychonaught at en.wikipedia 

Image: Cannabis indica.jpg Source: http://en.wikipedia.Org/w/index.php ?title=File:Cannabis_indica.jpg License: Free Art License Contributors: Axsadi Sanchez de Tagle 
FilerAnandamid.svg Source: http://en.wikipedia.org/w/index.php?title=File:Anandamid.svg License: Public Domain Contributors: NEUROtiker 

FilerSimple distillation apparatus.svg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Simple_distillation_apparatus.svg License: Public Domain Contributors: Original PNG by 
UsenQuantockgoblin, SVG adaptation by UsenSlashme 

File:Zosimosapparat.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Zosimosapparat.jpg License: Public Domain Contributors: Original uploader was Adragoor at sv.wikipedia 
FilerMy retort.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:My_retort.jpg License: Public domain Contributors: 6. Kjiac, Chatsam, Nk, Spiritia, Toto-tarou 
FilerAlembic.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Alembic.png License: Public Domain Contributors: H Padleckas, Jarekt, LeastCommonAncestor, Luigi Chiesa, Pjetter, 

1 anonymous edits 

File: UkrainianVodkaStill.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Ukrainian VodkaStill.jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: Arne 

Hiickelheim 

File : Dor f Lore - Schnaps-Destillation.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Dorf_Lore_-_Schnaps-Destillation.jpg License: GNU Free Documentation License 

Contributors: Hans-Peter Grumpe 

FilerBatchDistill.svg Source: http://en.wikipedia.org/w/index.php?title=File:BatchDistill.svg License: unknown Contributors: Original uploader was User Al at en.wikipedia. Later version(s) 
were uploaded by Xyzzy n at en.wikipedia. 

File:DDW.JPG Source: http://en.wikipedia.0rg/w/index.php ?title=File:DDW.JPG License: Creative Commons Attribution-Sharealike 3.0 Contributors: UsenGuruleninn 
FilerVacuum distillation of DMSO at 70C.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Vacuum_distillation_of _DMSO_at_70C.jpg License: Public Domain Contributors: 
Original uploader was Rifleman 82 at en.wikipedia 

Filerperkin triangle distillation apparatus.svg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Perkin_triangle_distillation_apparatus.svg License: Creative Commons Attribution- Share 
Alike Contributors: Original PNG by UsenQuantockgoblin, SVG adaptation by UsenSlashme 

Filershort path distillation apparatus.svg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Short_path_distillation_apparatus.svg License: Public Domain Contributors: Original PNG by 
UsenQuantockgoblin, SVG adaptation by UsenSlashme 

FilerColonne distillazione.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Colonne_distillazione.jpg License: Creative Commons Attribution 3.0 Contributors: User:Luigi Chiesa 
File: Continuous Binary Fractional Distillation.PNG Source: http://en.wikipedia.org/w/index.php?title=File:Continuous_Binary_Fractional_Distillation.PNG License: Creative Commons 
Attribution-ShareAlike 3.0 Unported Contributors: User:H Padleckas, UsenMbeychok, Usenmbeychok 

FilerBubble Cap Trays.PNG Source: http://en.wikipedia.org/w/index.php?title=File:Bubble_Cap_Trays.PNG License: Creative Commons Attribution-Sharealike 2.5 Contributors: H 
Padleckas created this image file in the middle of November 2006 for use in the article "Fractionating column" in Wikimedia. 

FilerVacuum Column.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Vacuum_Column.jpg License: GNU Free Documentation License Contributors: I do not know the name of 
the individual who actually took the photograph. 

File:Retort-in-operation-early-chemistry.PNG Source: http://en.wikipedia.org/w/index.php?title=File:Retort-in-operation-early-chemistry.PNG License: Public Domain Contributors: 
HappyApple, 2 anonymous edits 
File: Distillation of dry and oxygen-free toluene.jpg Source: http://en.w1kipedia.0rg/w/index.php ?title=File:Distillation_of_dry _and_oxygen-free_toluene.jpg License: Public Domain 

Contributors: Original uploader was Rifleman 82 at en.wikipedia 

FilerVacuum Column.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Vacuum_Column.png License: Public Domain Contributors: Mbeychok 
FilerRotavapor.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Rotavapor.jpg License: GNU Free Documentation License Contributors: Geni 

FilerSemi-microscale distillation.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Semi-microscale_distillation.jpg License: Public Domain Contributors: user:Rifleman_82 
FilerSandalwoodEssOil.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:SandalwoodEssOil.png License: Public Domain Contributors: Itineranttrader 
filerCommons-logo.svg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Commons-logo.svg License: logo Contributors: Anomie 

FilerDrop of cannabis oil.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Drop_of_cannabis_oil.jpg License: Creative Commons Attribution 2.5 Contributors: Ryan 
Bushby(HighlnBC) 

FilerHashoil.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Hashoil.jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: jlcoving (talk) 
FilerHemp extract fine.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Hemp_extract_fine.jpg License: Public Domain Contributors: Meco, Ravenhurst, Timeshifter 



Image Sources, Licenses and Contributors 69 

FilerGolden Cannabis Oil.JPG Source: http://en.wikipedia.Org/w/index.php ?title=File:Golden_Cannabis_Oil.JPG License: Public domain Contributors: H 

File: FullExtractCannabisOil.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:FullExtractCannabisOil.jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: 
UsenAnon lynx 

Image rCoflore ACX.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Coflore_ACX.png License: Creative Commons Attribution-Sharealike 3.0 Contributors: Echis 
File: Blackberry medical cannabis.jpg Source: http://en.w1kipedia.0rg/w/index.php ?title=File:Blackberry _medical_cannabis.jpg License: Creative Commons Attribution-Sharealike 3.0 
Contributors: User:Mjpresson 

FilerDrug bottle containing cannbis.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Drug_bottle_containing_cannbis.jpg License: Public Domain Contributors: Albertomos, 
Banana patrol, EL, Notwist, Olybrius, Photohound, Timeshifter, 3 anonymous edits 

Image:Cannab2 new.png Source: http://en.wikipedia.org/w/index.php?title=File:Cannab2_new.png License: Public Domain Contributors: UsenPhotohound derivative work: Cannab2.jpg: 
FilerCannabis sativa (Kohler).jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cannabis_sativa_(Kohler).jpg License: Public Domain Contributors: Hermann Adolf Kohler (1834 - 
1879) 

FilerWomen's Alliance For Medical Marijuana - Victoria.JPG Source: http://en.wikipedia.org/w/index.php?title=File:Women's_Alliance_For_Medical_Marijuana_-_Victoria.JPG License: 
Attribution Contributors: WAMM 

FilerCompassionl.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Compassionl.jpg License: Public Domain Contributors: Compassion007 

FilerMedical cannabis.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Medical_cannabis.jpg License: Public Domain Contributors: Medical.jpg: Coaster420 Purple_Goo.jpg: 
Coaster420 derivative work: Agent Agent (talk) 

FilerCannabis sativa (16).jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cannabis_sativa_(16).jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: 
UsenSevela.p 

FilerCannabis Clones in BoxJPG Source: http://en.wikipedia.org/w/index.php?title=File:Cannabis_Clones_in_Box.JPG License: Creative Commons Attribution-Sharealike 3.0 Contributors: 
UsenCannatraining 

FilerSKJ-cannabis.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File: SKJ-cannabis.jpg License: Creative Commons Attribution 2.0 Contributors: D-Kuru, FlickrLickr 
FilerCannabis sativa (6).jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cannabis_sativa_(6).jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: 
UsenSevela.p 

FilerCannabis sativa (9).jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cannabis_sativa_(9).jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: 
UsenSevela.p 

FilerCannabis sativa 01.JPG Source: http://en.wikipedia.org/w/index.php?title=File:Cannabis_sativa_01JPG License: Creative Commons Attribution-Sharealike 3.0 Contributors: 
AfroBrazilian 

FilerTetrahydrocannabinoLsvg Source: http://en.wikipedia.org/w/index.php?title=File:Tetrahydrocannabinol.svg License: Public Domain Contributors: Yikrazuul 

FilerCannabidiol.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cannabidiol.png License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: Benjah-bmm27, 
Cacycle 

FilerCannabinol.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cannabinol.png License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: BenrrlOl, Cacycle 
Filer Beta- Caryophyllen.svg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Beta-Caryophyllen.svg License: Public Domain Contributors: NEUROtiker (talk) 
FilerCannabigerol.png Source: http://en.wikipedia.org/w/index.php?title=File:Cannabigerol.png License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: Cacycle 
FilerAspergillus.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Aspergillus.jpg License: Public Domain Contributors: Aiko, Ixitixel, Photohound, Rasbak, Strobilomyces, 2 
anonymous edits 

FilerDa-ma.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Da-ma.png License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: Photohound 
FilerPEbers c41-bc.jpg Source: http://en.wikipedia.org/w/index.php?title=File:PEbers_c41-bc.jpg License: unknown Contributors: PEbers_c41.jpg: Einsamer Schiitze derivative work: 
Photohound (talk) 

Filer Cavalcade frieze Parthenon (1) BM.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cavalcade_frieze_Parthenon_(l)_BM.jpg License: Creative Commons 
Attribution-Sharealike 2.0 Contributors: Claire H. 

FilerCannabissativadior.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Cannabissativadior.jpg License: Public Domain Contributors: AnonMoos, Lewenstein, Nina-no, Pixeltoo, 
Wikiborg 

FilerMaltoscannabis.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Maltoscannabis.png License: Public Domain Contributors: Fizzle2007, Photohound, Timeshifter 
FilerCannabisAmericana JLHopkins B.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:CannabisAmericana_JLHopkins_B.jpg License: Public Domain Contributors: Arnaudh, 
Tekstman, Timeshifter 

FilerLegality of cannabis for medical purposes.png Source: http://en.wikipedia.0rg/w/index.php ?title=File:Legality_of_cannabis_for_medical_purposes.png License: Creative Commons 
Attribution-Sharealike 3.0 Contributors: UsenTrinitresque 

FilerCentre compassion de MontrealOlJPG Source: http://en.wikipedia.org/w/index.php?title=File:Centre_compassion_de_Montreal01.JPG License: Creative Commons 
Attribution-Sharealike 3.0,2.5,2.0,1.0 Contributors: Khayman 

FilerKccsreception.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Kccsreception.jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: UsenSubvertc 
Filer Professor Raphael Mechoulam.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Professor_Raphael_Mechoulam.jpg License: Attribution Contributors: en:User:Tzahy 
FilerBedica, medicinale cannabis flos 5 gram, granulaat.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Bedica,_medicinale_cannabis_flos_5_gram,_granulaat..jpg License: 
Creative Commons Attribution-Sharealike 3.0 Contributors: User:Medische-wiet 

FilerBedrocan, medicinale cannabis flos 5 gram.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Bedrocan,_medicinale_cannabis_flos_5_gram.jpg License: Creative Commons 
Attribution-Sharealike 3.0 Contributors: User:Medische-wiet 

FilerBediol, medicinale cannabis flos 5 gram, granulaat.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Bediol,_medicinale_cannabis_flos_5_gram,_granulaat..jpg License: 
Creative Commons Attribution-Sharealike 3.0 Contributors: User:Medische-wiet 

FilerBedrobinol, medicinale cannabis flos 5 gram.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Bedrobinol,_medicinale_cannabis_flos_5_gram.jpg License: Creative Commons 
Attribution-Sharealike 3.0 Contributors: User:Medische-wiet 

FilerDiscount Medical Marijuana - 2.jpg Source: http://en.wikipedia.0rg/w/index.php ?title=File:Discount_Medical_Marijuana_-_2.jpg License: Creative Commons Attribution-Sharealike 3.0 
Contributors: UsenO'Dea 

FilerUS-patent-6630507.pdf Source: http://en.wikipedia.org/w/index.php?title=File:US-patent-6630507.pdf License: Public Domain Contributors: Aidan J. Hampson, Julius Axelrod, Maurizio 
Grimaldi, The United States of America as represented by the Department of Health and Human Services 



License 70 



License 



Creative Commons Attribution-Share Alike 3.0 Unported 
//creativecommons.org/licenses/by-sa/3.0/